title string | abstract string | doi string | has_route int64 |
|---|---|---|---|
Large-Scale Synthesis of the Anti-Cancer Marine Natural Product (+)-Discodermolide. Part 2: Synthesis of Fragments C<sub>1</sub><sub>-</sub><sub>6</sub> and C<sub>9-14</sub> | Kilogram-scale syntheses of fragments C 1 - 6 ( 6 ) and C 9 - 14 ( 4 ) of (+)-discodermolide from common precursor 3 are described. Improved procedures for each step of both fragments were developed by minimizing or eliminating the formation of byproducts that were isolated and characterized in Smith's synthesis. | 10.1021/op0341317 | 1 |
Large-Scale Synthesis of the Anti-Cancer Marine Natural Product (+)-Discodermolide. Part 1: Synthetic Strategy and Preparation of a Common Precursor | The synthetic strategy for producing multigram quantities of (+)-discodermolide ( 1 ) using a hybridized Novartis−Smith−Paterson synthetic route via common precursor 3 is described. In the first part of this five-part series, we present a multikilogram preparation of α-methyl aldehyde 10 from Roche ester, its syn- aldo... | 10.1021/op034130e | 1 |
Environmentally Friendly and Efficient Process for the Preparation of β-Hydroxyl Ketones | An environmentally benign and efficient process for the preparation of β-hydroxyl ketones was developed by the practical cross-aldol reactions of 2-acetylpyridine, acetophenone, and cyclohexanone with 4-nitro-, 3-nitro-, and 2-nitrobenzaldehydes in water catalyzed by Na 2 CO 3 in very high yields. | 10.1021/op0341263 | 0 |
The Application of Microreactor Technology for the Synthesis of 1,2-Azoles | We demonstrate the successful synthesis of an array of 1,2-azoles within a borosilicate glass microreactor whereby conversions in the range of 98−100% were obtained. In terms of large-scale production, this corresponds to 0.339 g day - 1 per microreactor when employing reagent concentrations of 1.0 M. | 10.1021/op034125a | 0 |
Process Research, Development, and Pilot-Plant Preparation of Clofencet, a Novel Wheat Hybridizing Agent: Lewis Acid-Catalyzed Reaction of Ethyl Diazoacetate with 4-Chlorophenyl Hydrazonoacetaldehyde | Described are studies directed toward the chemical research and development of an alternative synthesis to 9, the penultimate intermediate of clofencet ( 1 ), a novel wheat-hybridizing agent. Retrosynthetic analyses as well as the results obtained from feasibility studies are detailed, leading to the successful develop... | 10.1021/op034123q | 1 |
Synthesis and Characterisation of Impurities of Manufacture in Support of Certificate of the European Pharmacopoeia Applications Part 1 (Clobetasone Butyrate) | Established pharmaceutical products often have complex supply chains and regulatory histories. In Europe the European Directorate for the Quality of Medicine (EDQM) (information from European Pharmacopoeia website, http://www.pheur.org/ ) have promoted the use of certificates of suitability of the European Pharmacopoei... | 10.1021/op0341216 | 0 |
Handbook of Reagents for Organic Synthesis: Chiral Reagents for Asymmetric Synthesis Edited by L. Paquette. Wiley: Chichester. 2003. 594 pp. £75. ISBN 0-4708-5625-4. | ADVERTISEMENT RETURN TO ISSUEPREVBook ReviewNEXTHandbook of Reagents for Organic Synthesis: Chiral Reagents for Asymmetric Synthesis Edited by L. Paquette. Wiley: Chichester. 2003. 594 pp. £75. ISBN 0-4708-5625-4.Cite this: Org. Proc. Res. Dev. 2003, 7, 6, 1085Publication Date (Web):September 6, 2003Publication History... | 10.1021/op034118m | 0 |
Synthesis of T2288: From Bench Synthesis to Pilot Production | A practical process to make N -(2,6-dimethylphenyl)-2-piperazin-1-yl-acetamide 1 is described, starting from piperazine 2 and N -chloroacetyl-2,6-xylidine 3 . The unwanted N, N ‘-bis-alkylated product 4 can be removed by simple filtration of the reaction mixture, while the excess of piperazine remains in the aqueous ph... | 10.1021/op034117u | 1 |
An Expedient Synthesis of LAF389, a Bengamide B Analogue | An optimized, convergent, safe synthesis of LAF389 ( 9 ), an anti-cancer agent analogous to bengamide B, is described. Starting from α- d -glucoheptonic ( d -glycero- d -gulo-heptonic acid) γ-lactone ( 10 ), the lactone 15 was constructed in five steps. Major improvements were made in the preparation of the aldehyde pr... | 10.1021/op0341162 | 1 |
A New Practical Route for the Manufacture of (4aR,10aR)-9-Methoxy-1-methyl-6-trimethylsilanyl- 1,2,3,4,4a,5,10,10a-octahydrobenzo[<i>g</i>]quinoline | Different synthetic routes to the enantiomerically pure octahydrobenzo[ g ]quinoline derivative JNZ092 were evaluated for their suitability to rapidly prepare a first clinical batch on a kilogram scale. On the basis of the experience of previous octahydrobenzo[ g ]quinoline projects a new linear synthesis of JNZ092 was... | 10.1021/op034112x | 1 |
The Synthesis of the High-Potency Sweetener, NC-00637. Part 3: The Glutamyl Moiety and Coupling Reactions | The synthesis of the high-potency sweetener, NC-00637 ( 1 ), required selective preparation of the γ-protected glutamic acid. Coupling of the three components could be performed in any order, but the final route involved N -acylation of the protected l -glutamic acid with the acid chloride derived from ( S )-2-methylhe... | 10.1021/op0341115 | 1 |
The Synthesis of the High-Potency Sweetener, NC-00637. Part 2: Preparation of the Pyridine Moiety | The pyridine moiety within the high-potency sweetener, NC-00637 ( 1 ), 5-amino-2-cyanopyridine ( 4 ), was prepared from 2-hydroxy-5-nitropyridine ( 10 ). The sequence involved the conversion of the hydroxy group to bromide followed by substitution with cyanide to give 2-cyano-5-nitropyridine ( 8 ). Reduction of the nit... | 10.1021/op034110c | 1 |
Crystallization Process Development of an Active Pharmaceutical Ingredient and Particle Engineering via the Use of Ultrasonics and Temperature Cycling | Process development of a Bristol-Myers Squibb drug substance candidate involved the development of crystallization and particle engineering protocols to address polymorphism, oiling out, and particle size control issues. Two monotropic polymorphs were evaluated, and one was determined to be thermodynamically more stabl... | 10.1021/op034107t | 0 |
Synthesis and Purification of 6-Ethoxy-4-oxo-1,4-dihydro-[1,5]naphthyridine-3-carboxylic Acid Benzylamide | The synthesis of 6-ethoxy-4-oxo-1,4-dihydro-[1,5]naphthyridine-3-carboxylic acid benzylamide ( 1 ) on multikilogram scale is described. The major challenge for the synthesis of this quinolone GABA partial agonist was in the isolation of product of acceptable purity for clinical studies due to the insolubility of this c... | 10.1021/op0341061 | 1 |
Safety vs Efficiency in the Development of a High-Energy Compound | A scalable route to 5-(2-carboxy-pyridin-2-yloxy)-benz[1,2,5]oxadiazole ( 3 ) is demonstrated. The synthesis was designed to minimize potential safety issues with a previously practiced route and, in particular, to avoid the handling of 5-hydroxybenzofurazan, which was found to decompose with a large energy release at ... | 10.1021/op0341059 | 1 |
Development of a Scalable Process for CI-1034, an Endothelin Antagonist | A concise, convergent multikilogram synthesis of CI-1034 (1 ), a potent endothelin receptor antagonist, is described. A 15-step preparation from commercially available o -vanillin and benzenesulfonyl chloride employs a remarkably robust Suzuki coupling between a boronic acid and an aromatic sulfonate ester as the key s... | 10.1021/op034104g | 1 |
A Practical Synthesis of the Platelet Fibrinogen Antagonist, Elarofiban | Elarofiban is a novel, nonpeptide, orally active fibrinogen receptor antagonist useful for the treatment of platelet mediated thrombotic disorders (Costanzo, M. J.; Hoekstra, W. J.; Maryanoff, B. E. WO, 97/41102, 1997). Herein we describe the process research that was carried out for the synthesis of elarofiban that ev... | 10.1021/op034103o | 1 |
A Comparison between Kinetic Parameters from the Synthesis of Tris(<i>p</i>-nitrophenyl)phosphite and Tris(<i>p</i>-nitrophenyl)phosphate Using Reaction Calorimetry | Tris( p -nitrophenyl)phosphite was prepared by a modification of a “one-pot” methodology developed for the preparation of triaryl phosphates. This exothermic reaction was performed in a Mettler RC-1 calorimeter. The principal aim of this work was to compare the reactivity of phosphorus trichloride and phosphorus oxychl... | 10.1021/op034100b | 0 |
Pilot Plant Preparation of an α<sub>v</sub>β<sub>3</sub> Integrin Antagonist. Part 1. Process Research and Development of a (<i>S</i>)-β-Amino Acid Ester Intermediate: Synthesis via a Scalable, Diastereoselective Imino-Reformatsky Reaction | Described are four process research investigations directed toward discerning a scalable, enantioselective method for preparing ( S )-β-amino acid ester 3, a key intermediate to the α v β 3 integrin antagonist 1 . Reported are an asymmetric Michael reaction approach, attempts to enantioselectively hydrogenate an enamin... | 10.1021/op034094j | 1 |
Practical Large-Scale Synthesis of Doripenem: A Novel 1β-Methylcarbapenem Antibiotic | A practical large-scale process for the synthesis of doripenem hydrate ( 1 ), a novel parenteral 1β-methylcarbapenem antibiotic, from p -nitrobenzyl-protected enolphosphate 2b and N -( p -nitrobenzyloxycarbonyl)-protected aminomethylpyrrolidine 3c is described. We found effective extraction conditions to remove p -tolu... | 10.1021/op034088n | 1 |
Electrostatic Hazards in Liquids and Relevance to Process Chemistry | Wherever there is flow of a liquid, there is the possibility of generating a static charge within it. The rate of flow, the conductivity of the liquid, and the diameter of the vessel/pipe have a dramatic effect on the electrostatic build up. Even though the system may be grounded, static charge can still accumulate and... | 10.1021/op0340863 | 0 |
CO<sub>2</sub> Offgas as a Mechanistic Probe and Scale-up Tool in N-Acylations Using Mixed Anhydrides from Amino Acids and Isobutyl Chloroformate | The reaction pathways of an N-acylation reaction, involving a mixed anhydride intermediate produced from reaction of an amino acid with isobutyl chloroformate, were analyzed using a novel technique involving the quantitation of CO 2 evolved during various parts of the process. Under the normal mode of addition, in whic... | 10.1021/op034085a | 0 |
A Scalable Synthesis of Meso-Substituted Dipyrromethanes | A one-flask synthesis of meso-substituted dipyrromethanes has been refined. The procedure entails reaction of an aldehyde in 100 equiv of pyrrole as the solvent containing a mild Lewis acid (e.g., InCl 3 ) at room temperature. Following removal and recovery of excess pyrrole, the dipyrromethane is obtained by crystalli... | 10.1021/op034083q | 0 |
A Convenient Synthesis of High-Purity 1-Chloro-2,6-difluorobenzene | A convenient preparation of high-purity 1-chloro-2,6-difluorobenzene has been developed. The key to the isolation of the desired isomer, without contamination of the difficult-to-separate isomer 1-chloro-2,3-difluorobenzene, is the use of sulfonyl chloride to direct fluorine substitution to the ortho and para positions... | 10.1021/op0340816 | 1 |
Software for Process Research, Development, and Scale-up | ADVERTISEMENT RETURN TO ISSUEEditorialNEXTSoftware for Process Research, Development, and Scale-upTrevor LairdView Author Information EditorCite this: Org. Proc. Res. Dev. 2003, 7, 4, 449Publication Date (Web):June 28, 2003Publication History Published online28 June 2003Published inissue 1 July 2003https://pubs.acs.org... | 10.1021/op034080d | 0 |
Practical Synthesis of <i>N</i>-{4-[(2-Methyl-4,5-dihydroimidazo[4,5-<i>d</i>][1]benzazepin- 6(1<i>H</i>)-yl)carbonyl]phenyl}biphenyl-2-carboxamide Monohydrochloride: an Arginine Vasopressin Antagonist | A novel, reliable, and cost-effective synthetic route to N -{4-[(2-methyl-4,5-dihydroimidazo[4,5- d ][1]benzazepin-6(1 H )-yl)carbonyl]phenyl}biphenyl-2-carboxamide monohydrochloride ( 1, YM087), a potent Arginine vasopressin antagonist, has been developed. Using moisture-controlled potassium carbonate, imidazole forma... | 10.1021/op034079e | 1 |
Rapid Scale-Up of the Matrix Metalloproteinase Inhibitor CH5902: Process Safety and Route Development Considerations | The synthesis of the novel MMP inhibitor CH5902 is described. In this approach, the original discovery route has been streamlined and telescoped into a four-stage sequence, which has been demonstrated on a multikilogram scale. A number of issues arising from both process development and process safety concerns are disc... | 10.1021/op0340762 | 1 |
Scalability of Microwave-Assisted Organic Synthesis. From Single-Mode to Multimode Parallel Batch Reactors | The direct scalability of microwave-assisted organic synthesis (MAOS) in a prototype laboratory-scale multimode microwave batch reactor is investigated. Several different organic reactions have been scaled-up typically from 1 mmol to 100 mmol scale. The transformations include multicomponent chemistries (Biginelli dihy... | 10.1021/op034075+ | 0 |
Process for Developing 3β-[4-(<i>S</i>)-Arylacetylamino-4β-(2-(2-furyl)ethyl]azetidin-2-one: A Carbacephem Key Intermediate | An optimized process for the stereospecific synthesis of carbacephem key intermediates 3β-[4-( S )-phenoxyacetylamino-4β-[2-(2-furyl)ethyl]azetidin-2-one ( 1 ) and 3β-[4-( S )-phenyl-acetylamino-4β-[2(2-furyl)ethyl)]azetidin-2-one] ( 2 ) is described. This report provides an efficient and cost-effective process for ach... | 10.1021/op034074h | 1 |
Reaction Safety: An Improved Procedure for the Preparation of 1,3,4,12a-Tetrahydro-11<i>H</i>-[1,4]-oxanio[3,4-<i>c</i>][1,4]benzodiazepine-6,12-dione with Iron in Acetic Acid | This contribution describes the development of an improved scaleable process to prepare 1,3,4,12a-tetrahydro-11 H -[1,4]-oxanio[3,4- c ][1,4]benzodiazepine-6,12-dione, 2, in a safe and operationally simple procedure using iron powder in acetic acid. The original procedure being used to prepare initial quantities of thi... | 10.1021/op034073p | 0 |
A Practical Synthesis of 6-[2-(2,5-Dimethoxyphenyl)ethyl]-4-ethylquinazoline and the Art of Removing Palladium from the Products of Pd-Catalyzed Reactions | A concise large-scale synthesis of 1, a new antimitotic agent is described. The key step was a one-pot Sonogashira cross-coupling of an aryl halide with a heteroaryl halide through an acetylene using the readily available 2-methyl-3-butyn-2-ol ( 7 ). An innovative approach for palladium removal was designed and success... | 10.1021/op034072x | 1 |
Evaluation and Optimisation of the Reagent Addition Sequence during the Synthesis of Atrazine (6-Chloro-<i>N</i><sup>2</sup>-ethyl-<i>N</i><sup>4</sup>-isopropyl-1,3,5-triazine-2,4-diamine) Using Reaction Calorimetry | The sequence of reagent addition and associated heats of reaction during the synthesis of the important herbicide atrazine (6-chloro- N 2 -ethyl- N 4 -isopropyl-1,3,5-triazine-2,4-diamine) from cyanuric chloride, isopropylamine, and ethylamine have been investigated by means of calorimetric and analytical methods. Sodi... | 10.1021/op0340715 | 0 |
A Scalable Synthesis of (<i>R</i>)-3,5-Dihydro-4<i>H</i>-dinaphth[2,1-<i>c</i>:1‘2‘-<i>e</i>]azepine | Environmentally benign scalable procedures are developed to supply enantiomerically pure ( R )-3,5-dihydro-4 H -dinaphth[2,1- c:1‘2‘- e ]azepine 1 as its hydrogen oxalate salt in a five-step overall yield of 41%, which consist of the following: (1) bis O -triflation of ( R )-1,1‘-bi-2-naphthol 8 [(CF 3 SO 2 ) 2 O, pyri... | 10.1021/op034067t | 0 |
The Process Development of a Novel Aldose Reductase Inhibitor, FK366. Part 1. Improvement of Discovery Process and New Syntheses of 1-Substituted Quinazolinediones | This contribution describes part 1 of process development of a novel aldose reductase inhibitor FK366 ( 1 ). The original process applied on a laboratory scale was improved from the safety viewpoint to manufacture materials on 500-L scale suitable for toxicological and pharmacological evaluations. A new process, includ... | 10.1021/op0340661 | 1 |
The Chemical Development of LB71350 | An efficient synthesis of the HIV-1 protease inhibitor LB71350 ( 1 ) is described. High diastereoselective epoxidation of the cis -allylic carbamate fragment of (5 S )-[ N -(benzyloxycarbonyl)-amino]- N -[2-methyl-(1 R )-[(phenyl)carbonyl]-propyl]-6-phenylhex-( Z )-enamide ( 16 ) and one-pot preparation of N -[(1-methy... | 10.1021/op034062w | 1 |
An Efficient and Cost-Effective Synthesis of Pagoclone | The compound (+)-2-(7-chloro-1,8-naphthyridin-2-yl)-3 S -(5-methyl-2-oxohexyl)-1-isoindolinone (pagoclone) shows anxiolytic activity due to partial agonism of the benzodiazepine site of the GABA A receptor. We describe the development of an economical and practical process for a 100+ kg pilot plant production used to s... | 10.1021/op034060b | 1 |
Process Development and Pilot Plant Scale Synthesis of Spiro[3.5]nonane-6,8-dione | A two step synthesis of spiro[3.5]nonane-6,8-dione is reported which allows the production of the target molecule on a pilot plant scale. The first step of the process comprises the epoxidation of spiro[3.5]non-7-en-6-one mediated by sodium perborate. Here, the use of sodium perborate proved beneficial over the standar... | 10.1021/op0340560 | 1 |
Safety Aspects of the Under-Pressure Reaction of Trichloroacetyl Chloride and Acrylonitrile in the Preparation of 3,5,6-Trichloro-2-pyridinol | The under-pressure reaction of trichloroacetyl chloride ( 1 ) with acrylonitrile ( 2 ) in the preparation of 3,5,6-trichloro-2-pyridinol becomes explosive in certain circumstances. The studies of the reaction's enthalpy, the instability of the 2-chloropropionitrile ( 8 ), and the observation of the unexpected increase ... | 10.1021/op0340558 | 0 |
An Efficient One-Pot Process for 10-Bromo-8-chloro-5,6-dihydro-benzo[5,6]cyclohepta[1,2-<i>b</i>]pyridin-11-one, an Intermediate to SCH 66336 | An efficient process for the preparation of 10-bromo-8-chloro-5,6-dihydro-benzo[5,6]cyclohepta[1,2- b ]pyridin-11-one ( 7), an intermediate to an antitumor agent SCH 66336, is described. This one-pot method consists of a selective reduction of 8-chloro-7(9)-nitro-5,6-dihydro-benzo[5,6]cyclohepta[1,2- b ]pyridin-11-one ... | 10.1021/op034054f | 1 |
Solvent-Free Organic Synthesis By K. Tanaka. Wiley−VCH: Weinheim. 2003. 433 pp. £80. ISBN 3-527-30612-9. | null | 10.1021/op034052v | 0 |
Process Development and Scale-Up of the PPAR Agonist NNC 61-4655 | A scalable synthetic route of the nonselective but PPARα-preferring potent PPAR agonist NNC 61 - 4655 aimed for treatment of type 2 diabetes was developed. The synthetic pathway comprises the convergent synthesis and coupling of the two key intermediates E -5-(chloropent-3-en-1-ynyl)benzene 8 (prepared in a five-step s... | 10.1021/op034048j | 1 |
Cross-Coupling Methods for the Large-Scale Preparation of an Imidazole−Thienopyridine: Synthesis of [2-(3-Methyl-3H-imidazol-4-yl)- thieno[3,2-<i>b</i>]pyridin-7-yl]-(2-methyl-1H-indol-5-yl)-amine | The multihundred-gram synthesis of [2-(3-methyl-3H-imidazol-4-yl)-thieno[3,2- b ]pyridin-7-yl]-(2-methyl-1H-indol-5-yl)-amine ( 1 ) is described utilizing a Stille cross-coupling of an iodothienopyridine ( 3 ) with 5-(tributylstannyl)-1-methylimidazole ( 11 ). Several cross-coupling methods were evaluated for the conve... | 10.1021/op0340457 | 1 |
Catalysts and Process for the Production of Benzyl Toluenes | A method for the synthesis of benzyl toluenes from toluene and using molecular bromine as catalytic operator is reported here. The process can be carried out in one of two ways: the first method involves the simultaneous bromination/alkylation of toluene, followed by recycling of the liberated HBr to an oxidation react... | 10.1021/op034043m | 0 |
Practical Large-Scale Synthesis of the 2-Aminomethylpyrrolidin-4-ylthio-Containing Side Chain of the Novel Carbapenem Antibiotic Doripenem | The first synthesis using an original procedure and a practical large-scale process using an improved procedure for the synthesis of the N -PNZ-protected 2-aminomethylpyrrolidin-4-ylthio-containing side chain of doripenem hydrate (S-4661), a novel parenteral 1β-methylcarbapenem antibiotic, are described. trans -4-Hydro... | 10.1021/op0340412 | 1 |
Developing an Industrial Chemical Process: An Integral Approach By J. Mizrahi. CRC Press: Boca Raton, FL. 2002. 229 pp. $140 (Paperback). ISBN 0-8493-1360-0. | null | 10.1021/op034039a | 0 |
Organolithiums: Selectivity for Synthesis By J. Clayden. Elsevier: the Netherlands. 2002. 384 pp. $125. ISBN 0-08-043262X. $45 (Paperback). ISBN 0-08-0432611. | ADVERTISEMENT RETURN TO ISSUEPREVBook ReviewOrganolithiums: Selectivity for Synthesis By J. Clayden. Elsevier: the Netherlands. 2002. 384 pp. $125. ISBN 0-08-043262X. $45 (Paperback). ISBN 0-08-0432611.Cite this: Org. Proc. Res. Dev. 2003, 7, 3, 448Publication Date (Web):April 9, 2003Publication History Published onlin... | 10.1021/op034038i | 0 |
Chemical Development on the Chiral Auxiliary (<i>S</i>)-4-(Phenylmethyl)-2-oxazolidinone Utilizing Automated Synthesis and DoE | Enantiopure 4-substituted oxazolidinones are well-known chiral auxiliaries for asymmetric synthesis of carboxylic acid derivatives. The 4-(phenylmethyl)-substituted oxazolidinones derived from d - or l -phenylalanine are known to be particularly useful. We have conducted chemical development studies toward an efficient... | 10.1021/op034033l | 0 |
Scale-Up of the Synthesis of a Pyrimidine Derivative Directly on Solid Support | The solid-phase synthesis of 4-(2-amino-6-phenylpyrimidin-4-yl)benzamide, a compound obtained through combinatorial chemistry and parallel synthesis, can be scaled up directly on solid support in excellent yields and high purity. By applying highly loaded aminomethyl polystyrene as solid support, a good ratio between t... | 10.1021/op034032t | 1 |
Concepts of Nature in Organic Synthesis: Cascade Catalysis and Multistep Conversions in Concert | The development of cascade conversions (i.e. combined (catalytic) reactions without intermediate recovery steps as taking place in living cells) is considered as one of the important future directions for carrying out sustainable organic syntheses with inherently safer designs. It will drastically reduce operating time... | 10.1021/op0340311 | 0 |
A Practical Synthesis of 3-<i>n</i>-Propylphenol, a Component of Tsetse Fly Attractant Blends | A practical synthesis of the tsetse fly attractant 3- n -propylphenol involves the Grignard reaction of 3-hydroxybenzaldehyde and ethylmagnesium bromide affording a benzylic alcohol-type phenol derivative that upon catalytic hydrogenation gives the title product in 75% overall yield. Selection of the right solvent mixt... | 10.1021/op0340309 | 1 |
Strictly “Pair”-Selective and Economical Synthesis of Conjugated Diynes via Pd-Catalyzed Reaction of Terminal Alkynes with 1,1-Dichloroethylene, Elimination with LDA, and Subsequent Transformations | Various unsymmetrically substituted conjugated diynes can be synthesized in a completely “pair”-selective manner via Pd-catalyzed reaction of terminal alkynes with 1,1-dichloroethylene in the presence of Pd(PPh 3 ) 4 followed by elimination with 2 equiv of lithium diisopropylamide (LDA), zincation with ZnBr 2 or ZnCl 2... | 10.1021/op034029+ | 0 |
The Synthesis of <i>N</i>-Aryl-5(<i>S</i>)-aminomethyl-2-oxazolidinone Antibacterials and Derivatives in One Step from Aryl Carbamates | Since 1993, a significant process research and development effort directed towards the large-scale synthesis of oxazolidinone antibacterial agents has been ongoing in both Early Chemical Process Research and Development, and Chemical Process Research and Development at Pharmacia. This work has led to the successful dev... | 10.1021/op034028h | 1 |
Identification and Control of a Process-Related Impurity in the Chlorination of 3-Hydroxy-3-carbacephem | A process for the synthesis of carbacephem key intermediate (4-nitrophenyl)methyl,7-amino-1-carba(dethia)-3-chloro-3-cephem-4-carboxylate, monohydrochloride (1 ) via chlorination and deacylation employing chlorotriphenoxyphosphonium chloride [(PhO) 3 P + ClCl - ] has been described. The most difficult problem encounter... | 10.1021/op034026x | 0 |
The Development of a Manufacturing Route for the GPIIb/IIIa Receptor Antagonist SB-214857-A. Part 1: Synthesis of the Key Intermediate 2,3,4,5-Tetrahydro-4-methyl-3-oxo-1<i>H</i>-1,4-benzodiazepine-2-acetic Acid Methyl Ester, SB-235349 | The development of an efficient manufacturing route to 2,3,4,5-tetrahydro-4-methyl-3-oxo-1 H -1,4-benzodiazepine-2-acetic acid methyl ester SB-235349, a key intermediate in the synthesis of lotrafiban is described. The synthesis starts with 2-nitrobenzyl alcohol which is mesylated, reacted with methylamine and then dim... | 10.1021/op034024c | 1 |
The Development of a Manufacturing Route for the GPIIb/IIIa Receptor Antagonist SB-214857-A. Part 2: Conversion of the Key Intermediate SB-235349 to SB-214857-A | The process development to the manufacturing route to (2 S )-7-([4,4‘-bipiperidin]-1-ylcarbonyl)-2,3,4,5-tetrahydro-4-methyl-3-oxo-1 H -1,4-benzodiazepine-2-acetic acid hydrochloride (SB-214857-A, lotrafiban) is described. The starting point is the previously reported intermediate (2 RS )-2,3,4,5-tetrahydro-4-methyl-3-... | 10.1021/op034023k | 1 |
Ionic Liquids in Synthesis Edited by P. Wasserscheid and T. Welton. Wiley-VCH: Weinheim. 2003. xvi + 364 pp. £80. ISBN 3-527-30515-7. | ADVERTISEMENT RETURN TO ISSUEPREVBook ReviewIonic Liquids in Synthesis Edited by P. Wasserscheid and T. Welton. Wiley-VCH: Weinheim. 2003. xvi + 364 pp. £80. ISBN 3-527-30515-7.Cite this: Org. Proc. Res. Dev. 2003, 7, 2, 223–224Publication Date (Web):February 26, 2003Publication History Published online26 February 2003... | 10.1021/op0340210 | 0 |
A Scalable Asymmetric Synthesis of (<i>R</i>)-2-Amino-1-(3-pyridinyl)ethanol Dihydrochloride via an Oxazaborolidine Catalyzed Borane Reduction | This report describes a scalable process for the asymmetric synthesis of ( R )-2-amino-1-(3-pyridinyl)ethanol dihydrochloride. The stereochemistry of the product is set via a reduction of 3-chloroacetyl pyridine with 2 equiv of borane-dimethyl sulfide and a catalytic amount of an in situ generated oxazaborolidine. The ... | 10.1021/op0340208 | 1 |
SYNPHOS: a New Atropisomeric Diphosphine Ligand. From Laboratory-scale Synthesis to Scale-up Development | A new optically active diphosphine ligand, [(5,6),(5‘,6‘)-bis(ethylenedioxy)biphenyl-2,2‘-diyl]bis(diphenylphosphine) (SYNPHOS) has been synthesized. Laboratory-scale synthesis and scale-up development of this ligand are described herein. This new atropisomeric diphosphine was also used in ruthenium-catalyzed asymmetri... | 10.1021/op034016w | 1 |
There's No Industrial Biocatalyst Like Hydrolase: Development of Scalable Enantioselective Processes Using Hydrolytic Enzymes<sup>1</sup> | Chiral, racemic esters, ethyl (±)-tetrahydrofuran-2-carboxylate 4c, methyl (±)-α-phenylpropionate 9b, methyl (±)-5,5-dimethyl-1,3-thiazolidine-4-carboxylate 12a, 2-methoxyethyl (±)-1-(4- tert -butylphenyl)-2-oxopyrrolidine-4-carboxylate 15a, (±)-1-benzyloxy-3-chloropropan-2-yl hydrogen succinate 18c, and (±)-3-butyrylo... | 10.1021/op034014b | 1 |
The Pilot Plant Real Book - A Unique Handbook for the Chemical Process Industry By Francis X. McConville. FXM Engineering and Design: Worcester, MA (http://www.pprbook.com). 2002. 312 pp. Price $89.95. ISBN 0-9721769-1-8. | ADVERTISEMENT RETURN TO ISSUEPREVBook ReviewNEXTThe Pilot Plant Real Book - A Unique Handbook for the Chemical Process Industry By Francis X. McConville. FXM Engineering and Design: Worcester, MA (http://www.pprbook.com). 2002. 312 pp. Price $89.95. ISBN 0-9721769-1-8.Will WatsonView Author Information Scientific Updat... | 10.1021/op034013j | 0 |
Process Development of ONO-2506: A Therapeutic Agent for Stroke and Alzheimer's Disease | A process for the synthesis of ONO-2506, an agent that suppresses astrocyte activation, has been developed. Significant improvement of the level of impurities in the final product has been achieved compared with the laboratory-scale procedure. Kilogram quantities of the compound have been supplied for preclinical studi... | 10.1021/op034008f | 1 |
Practical Preparation and Resolution of 1-(2‘-Diphenylphosphino-1‘-naphthyl)isoquinoline: A Useful Ligand for Catalytic Asymmetric Synthesis | A practical synthesis of the atropisomerically chiral ligand QUINAP is described, followed by its efficient resolution into enantiomers by employing a deficiency of the chloropalladium complex derived from 1‘ -(R)- 1‘-(dimethylamino)-1-ethylnaphthalene. The X-ray structure of the ligand, which crystallises as a conglom... | 10.1021/op034007n | 1 |
Efficient Enantioselective Synthesis of the NMDA 2B Receptor Antagonist Ro 67-8867 | An efficient, enantioselective, and scalable eight-step synthesis for the NMDA 2B receptor antagonist Ro 67-8867 ( S, S )- 1 selected for the treatment of acute ischemic stroke is described based on the coupling reaction of the amino alcohol ( S, S )- 6 with the sulfone building block 7. The synthesis of the amino alco... | 10.1021/op034006v | 1 |
Asymmetric Synthesis of an MMP-3 Inhibitor Incorporating a 2-Alkyl Succinate Motif | An efficient and practical synthesis is presented of the pharmaceutically active MMP-3 inhibitor UK-370,106 ( 1 ) via an olefination/catalytic asymmetric hydrogenation sequence. Commercially available 5-bromo-2-iodotoluene was converted in two steps to the biarylpropanal equivalent ( 11 ), which was reacted with the ph... | 10.1021/op034001y | 1 |
Overcoming Backpressure Problems during Solid-Phase Synthesis of Oligonucleotides | During solid-phase synthesis of oligonucleotides in packed-bed reactors a substantial pressure build-up is observed during acid deprotection and subsequent solvent washing as the length of the support-bound oligonucleotide increases. Maintaining high flow rates of reagents and wash solvents is crucial to achieving the ... | 10.1021/op030213j | 0 |
Preparation of Guanine PDE Inhibitors: Development of the Common Synthetic Route Strategy. A Case Study | A single synthetic route, called the chloropurine route, capable of quickly delivering initial kilogram quantities of several chiral as well as achiral guanine phosphodiesterase inhibitors of increasing complexity is described. During the course of this work, unraveling the formation mechanism of chloropurines allowed ... | 10.1021/op030212r | 1 |
Research and Development of a Second-Generation Process for Oseltamivir Phosphate, Prodrug for a Neuraminidase Inhibitor | A second-generation manufacturing process from a shikimic acid-derived epoxide to oseltamivir phosphate features a magnesium chloride−amine complex-catalyzed ring opening of the epoxide by tert -butylamine, a selective O-sulfonylation of the resulting tert -butylamino alcohol, a surprisingly efficient cleavage of a ter... | 10.1021/op0302107 | 1 |
Process Research on [(2<i>S</i>)-(3-Fluorophenyl)-(1<i>S</i>)-(5-oxotetrahydrofuran- 2-yl)ethyl]carbamic Acid <i>tert</i>-Butyl Ester, a Lactone Intermediate for an Aspartyl Protease Inhibitor | Two processes for the preparation of lactone [2 S -(3-fluorophenyl)-1 S -(5-oxotetrahydrofuran-2-yl)ethyl]carbamic acid tert -butyl ester 1 starting from S -BOC-(3-fluorophenyl)alanine 3 are described. ( S )-(3-Fluorophenyl)alanine N -methyl- N -methoxy amide 10, the Weinreb amide of 3, was reacted with 2-(2-1,3-dioxan... | 10.1021/op030207n | 1 |
Process Research of (<i>R</i>)-Cyclohexyl Lactic Acid and Related Building Blocks: A Comparative Study | ( S )-Cyclohexyl lactic acid is a component of the selective E-selectin inhibitor 2 (( S )-cHexLact-2- O -(3-Galβ(1→3)ddGlc(4→1)αFuc). We describe the evaluation of various synthetic routes to this building block: ( A ) diazotation of phenylalanine followed by phenyl ring hydrogenation; ( B ) phenyl ring hydrogenation ... | 10.1021/op030202q | 1 |
A Practical Pilot-Scale Synthesis of 4-Vinyl-2,3-dihydrobenzofuran Using Imidate Ester Chemistry and Phase-Transfer Catalysis | A two-step telescoped synthesis of 4-vinyl-2,3-dihydrobenzofuran ( 2 ) was demonstrated using imidate ester chemistry and phase-transfer catalysis. Treatment of 2,3-bis(2-hydroxyethyl)phenol ( 1 ) with the Vilsmeier reagent resulted in an in situ generation of a bis-imidate intermediate 4, which was converted to 4-(2-c... | 10.1021/op030201y | 1 |
Polymeric Materials in Organic Synthesis and Catalysis Edited by Michael R. Buchmeiser. Wiley Interscience: Weinheim. 2003. xxxiii + 559 pp. 159 Euro/235 SFR. ISBN 3-527-30630-7. | ADVERTISEMENT RETURN TO ISSUEPREVBook ReviewNEXTPolymeric Materials in Organic Synthesis and Catalysis Edited by Michael R. Buchmeiser. Wiley Interscience: Weinheim. 2003. xxxiii + 559 pp. 159 Euro/235 SFR. ISBN 3-527-30630-7.Philip HodgeView Author Information Department of Chemistry, University of Manchester, Oxford ... | 10.1021/op030052j | 0 |
The Merck Bile Acid Cortisone Process: The Next-to-Last Word | A personal account of the process research and development effort at Merck and Company, leading to the first commercial process for the manufacture of cortisone acetate, is described. | 10.1021/op030050z | 1 |
A Practical Synthesis of 2,3,4,6-Tetra-<i>O</i>-acetyl-1-<i>O</i>-(2-propenyl)-β-<scp>d</scp>-glucopyranoside Using ZnCl<sub>2</sub> | 2,3,4,6-Tetra- O -acetyl-1- O -(2-propenyl)-β- d -glucopyranoside ( 1a ), which is a useful raw material in the synthesis of a bioactive agent, has been synthesized in 50% yield by reacting β- d -glucose pentaacetate and 3 mol equiv of an allyl alcohol with 0.9 mol equiv of ZnCl 2 in toluene at 80 °C for 2 h followed b... | 10.1021/op0300488 | 0 |
Chromatography as an Enabling Technology in Pharmaceutical Process Development: Expedited Multikilogram Preparation of a Candidate HIV Protease Inhibitor | Chromatography plays a vital role in supporting preclinical pharmaceutical development, whether in providing assays for purity determinations, preparative separation of small amounts of intermediates for route selection studies, or purification of bulk drug substances on multikilogram scale. All three approaches are il... | 10.1021/op0300443 | 0 |
Calorimetric Approach and Simulation for Scale-Up of a Friedel−Crafts Reaction | The present study, on the optimisation of the scale-up of a Friedel−Crafts acylation, joins together experimental calorimetric techniques and simulation techniques. The adopted methodology involved the execution of isothermal tests at different temperatures, using the reaction calorimeter RC1, to obtain the heat flow v... | 10.1021/op030043a | 0 |
A New Approach to the Rapid Parallel Development of Four Neurokinin Antagonists. Part 5. Preparation of ZM374979 Cyanoacid and Selective Crystallisation of ZM374979 Atropisomers | ZM374979 cyanoacid was prepared from ZD4974 cyanoester by a selective Grignard reaction followed by selective ester hydrolysis. On conversion of ZM374979 cyanoacid to ZM374979 free base, atropisomerism was observed, necessitating the development of a process for the selective crystallisation of a single atropisomer. | 10.1021/op030041q | 1 |
A New Approach to Rapid Parallel Development of Four Neurokinin Antagonists. Part 4. Synthesis of ZD2249 Methoxy Sulfoxide | The manufacture of ZD2249 methoxy sulfoxide ( 1 ) using a new project approach is described. Research department processes were scaled up to 100 L if process safety and robustness were not compromised; other factors were treated according to the new approach. Using this strategy, we were able to manufacture a key inter... | 10.1021/op030039z | 1 |
Evaluation of Kinetic Parameters from the Synthesis of Triaryl Phosphates Using Reaction Calorimetry | ADVERTISEMENT RETURN TO ISSUEPREVAddition/CorrectionNEXTORIGINAL ARTICLEThis notice is a correctionEvaluation of Kinetic Parameters from the Synthesis of Triaryl Phosphates Using Reaction CalorimetryCarlos F. Pinto Machado e Silva and Joao F. Cajaiba da SilvaCite this: Org. Proc. Res. Dev. 2003, 7, 6, 1083Publication D... | 10.1021/op0300387 | 0 |
An Efficient Synthesis of a Key Intermediate for the Biologically Active Vitamin D Analogue, Seocalcitol | In the key synthetic step in the manufacture of the key intermediate for the biologically active vitamin D analogue, seocalcitol, a more practical and attractive procedure is achieved using the commercially available EtMgBr and CeCl 3, resulting in 79% yield. The key intermediate is synthesised from vitamin D 2 in 10 s... | 10.1021/op030037e | 1 |
Stereoselective Synthesis of Alkylphosphonates: A Facile Rearrangement of Cyanoethyl-Protected Nucleoside Phosphoramidites | Cyanoethyl-protected nucleoside phosphoramidites undergo a facile Michaelis−Arbuzov reaction upon addition of acrylonitrile to afford cyanoethyl phosphonates. This rearrangement is stereoselective at room temperature, but racemization is observed at high temperatures, indicating two different pathways. A plausible mech... | 10.1021/op030035u | 0 |
A New Multipurpose Microreactor for Process Safety Studies | A new glass-lined microreactor for SETARAMs Calvet Calorimeters BT 2.15 and C 80 is described, which allows fast and simple characterization of thermal properties of chemical reactions and reaction mixtures. Application examples are presented, and the special features of this reactor are outlined. | 10.1021/op030030x | 0 |
Optimisation of Ethyl(2-phthalimidoethoxy)acetate Synthesis with the Aid of DOE | We investigated the reaction of alkylation of 2-phthalimidoethanol with ethyl chloroacetate leading to ethyl(2-phthalimidoethoxy)acetate. The synthesis was successfully optimised by applying factorial design. Major side products have been separated, identified, and characterised. The yield level was increased from 25% ... | 10.1021/op030029y | 0 |
Optimization of the Reduction of a 5-Benzylidenethiazolidine-2,4-dione Derivative Supported by the Reaction Response Surface Analysis: Synthesis of Pioglitazone Hydrochloride | A reaction response surface analysis was applied to a series of experiments carried out under various conditions (temperature, time, amount of a catalyst and reduction reagents, purification of the substrate). Significant improvements were made in the C C bond reduction in the benzylidene−thiazolidinedione intermediate... | 10.1021/op0300286 | 0 |
Efficient Preparation of a Key Intermediate in the Synthesis of Roxifiban by Enzymatic Dynamic Kinetic Resolution on Large Scale | Additional information is presented for the transformation of a kinetic resolution into a dynamic kinetic resolution of the isobutyl ester 5b to form the acid 2 in high yield and ee via the intermediacy of a thioester 6c, (Pesti, J. A.; Yin, J.; Zhang, L.-H; Anzalone, L. J. Am. Chem. Soc. 2001, 123, 11075−11076.). The ... | 10.1021/op0300239 | 0 |
Combined Effect of Polymorphism and Process on Preferential Crystallization: Example with (±)-5(4‘-Methylphenyl)-5-methylhydantoin | The structural data of two varieties of the title compound as well as the corresponding irreversible polymorphic transition are detailed. Although extensive structural analogies are pointed out, the transition is of destructive/reconstructive type with a poor rate requiring days or even weeks for completion. Without se... | 10.1021/op030022g | 0 |
Online Spectroscopic Investigations (FTIR/Raman) of Industrial Reactions: Synthesis of Tributyltin Azide and Hydrogenation of Chloronitrobenzene | The utilization of online spectroscopic methods (FTIR/Raman) for the development and the monitoring of chemical processes was demonstrated with two important chemical reaction types. The synthesis of tri- n -butyltin azide takes place at the solid−liquid interface and is therefore very sensitive to changes of reaction ... | 10.1021/op030009w | 0 |
Continuous Process for the Production of Aromatic Hydrocarbons from <i>n</i>-Hexane and C<sub>5+</sub> Natural Gas Liquid over Pd-Loaded ZSM-5 Zeolite | A continuous process for the production of aromatic hydrocarbons from n -hexane and C 5+ natural gas liquid (C 5+ NGL) over Pd-loaded ZSM-5 zeolite in a tubular reactor was developed. The optimal conditions for continuous aromatization of n -hexane and C 5+ NGL were found at 400 °C reaction temperature and 0.4 cm 3 /mi... | 10.1021/op030007b | 0 |
Efficient Synthesis of Antisense Phosphorothioate Oligonucleotides: Evaluation of Dichloroacetic Acid at Higher Concentration to Reduce Cycle Time | Efficiency of phosphorothioate oligonucleotide syntheses could be improved by increasing the concentration of dichloroacetic acid in toluene to 10% from 3% (v/v) during the detritylation step. It was also found that dichloroacetic acid is better than dichloropropionic acid when compared at similar concentrations. | 10.1021/op030006j | 0 |
Development of the Juliá−Colonna Asymmetric Epoxidation Reaction: Part 1. Preparation and Activation of the Polyleucine Catalyst | The preparation of silica-supported poly- l -leucine has been studied under a variety of reaction conditions leading to an efficient procedure for the preparation of material suitable for use in the Juliá−Colonna asymmetric epoxidation reaction. | 10.1021/op0300037 | 0 |
Synthesis and Chemistry of Agrochemicals VI Edited by D. R. Baker, J. G. Fenyes, G. P. Lahm, T. P. Selby, and T. M. Stevenson. ACS Symposium Series 800. American Chemical Society: Washington, DC (Distributed by Oxford University Press). 2002. xii + 364 pp. £95/$135.00. ISBN 0-8412-3783-2. | ADVERTISEMENT RETURN TO ISSUEPREVBook ReviewNEXTSynthesis and Chemistry of Agrochemicals VI Edited by D. R. Baker, J. G. Fenyes, G. P. Lahm, T. P. Selby, and T. M. Stevenson. ACS Symposium Series 800. American Chemical Society: Washington, DC (Distributed by Oxford University Press). 2002. xii + 364 pp. £95/$135.00. IS... | 10.1021/op030001m | 0 |
Development of Jacobsen Asymmetric Epoxidation and Sharpless Asymmetric Dihydroxylation Methods for the Large-Scale Preparation of a Chiral Dihydrobenzofuran Epoxide | Two well-known methodologies, the Jacobsen asymmetric epoxidation (AE) and the Sharpless asymmetric dihydroxylation (AD) followed by epoxidation, were evaluated for the large-scale preparation of a chiral dihydrobenzofuran epoxide. The AE method was improved by substituting ethanol for dichloromethane for the dissoluti... | 10.1021/op025622e | 0 |
Process Development for a Herbicide Intermediate via Catalytic Carboxylation of an Aromatic Diazonium Compound | A laboratory process is described for the preparation of 2-sulfo-4-methoxybenzoic acid (SMBA) via diazotization of 2-amino-4-methoxy-sulfonic acid followed by Pd-catalyzed carbonylation in the presence of water. The most important process parameters were the catalyst precursor and water content. Both a two-step procedu... | 10.1021/op025621m | 1 |
The Synthesis of OSU 6162: Efficient, Large-Scale Implementation of a Suzuki Coupling | The synthesis of the chiral, nonracemic 3-aryl piperidine, OSU 6162 ( 1 ), a potential CNS agent from Pharmacia Corporation, is presented. The key construction in the described synthesis is a palladium-catalyzed aryl cross-coupling reaction between bromosulfone ( 4 ) and pyridyl borane ( 14 ). Initially developed condi... | 10.1021/op025620u | 1 |
Process Optimization and Synthesis of 3-(4-Fluorophenyl)-4,5-dihydro-<i>N</i>-[4-(tri- fluoromethyl)phenyl]-4-[5-(trifluoromethyl)-2-pyridyl]-1<i>H</i>-pyrazole-1-carboxamide | ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTProcess Optimization and Synthesis of 3-(4-Fluorophenyl)-4,5-dihydro-N-[4-(tri- fluoromethyl)phenyl]-4-[5-(trifluoromethyl)-2-pyridyl]-1H-pyrazole-1-carboxamideJames M. Renga, Kevin L. McLaren, and Michael J. RicksView Author Information Discovery Process Research, Dow AgroSc... | 10.1021/op025619v | 1 |
Thermochemical Scale-Up of a Mesylation Reaction | The scale-up of the synthesis of a very expensive key pharmaceutical intermediate requires a very accurate knowledge of the overall heat-transfer coefficient of the plant reactors. Those data allow the optimization of the safety, quality, and yield of the process. Starting from the accurate and reliable measurements de... | 10.1021/op025617a | 0 |
The Synthesis of the High-Potency Sweetener, NC-00637. Part 1: The Synthesis of (<i>S</i>)-2-Methylhexanoic Acid | The synthesis of the high potency sweetener candidate NC-00637 ( 1 ) required large quantities of ( S )-2-methylhexanoic acid ( 2 ). This acid was first prepared in small quantities by the use of chiral auxiliaries. For large quantities, resolution by classical means and an enzymatic method were investigated. Asymmetri... | 10.1021/op025616i | 1 |
Large-Scale Negishi Coupling as Applied to the Synthesis of PDE472, an Inhibitor of Phosphodiesterase Type 4D | 5-[2-Methoxy-5-(4-pyridinyl)phenyl]-2,1,3-benzoxadiazole (PDE472) is a selective inhibitor of the phosphodiesterase PDE4D isoenzyme, which is a recognised drug target for the treatment of asthma. Different synthetic routes to PDE472 were investigated, and the research synthesis was optimised to prepare a phase I batch ... | 10.1021/op025615q | 1 |
May <i>Organic Process Research & Development</i> Keep Growing! | ADVERTISEMENT RETURN TO ISSUEEditorialNEXTMay Organic Process Research & Development Keep Growing!View Author Information EditorCite this: Org. Proc. Res. Dev. 2003, 7, 1, 1Publication Date (Web):December 19, 2002Publication History Published online19 December 2002Published inissue 1 January 2003https://doi.org/10.1021... | 10.1021/op025614y | 0 |
The Asymmetric Synthesis of (3<i>S</i>,4<i>R</i>,5<i>S</i>)-3-Amino-4,5-<i>O</i>-isopropylidenedioxycyclopentene | The title amine, an important substructure of nucleoside Q, is available from the 3,4-epoxycyclopentene in five steps. The epoxide is directly converted to the acetonide of cis -3, 4-dihydroxycyclopentene by treatment with boron trifluoride, a ring-opening with retention of configuration, a previously unknown process s... | 10.1021/op025611l | 1 |
Reinvestigation of the Reaction of Trichloroacetyl Chloride and Acrylonitrile in the Preparation of 3,5,6-Trichloropyridin-2-ol | The synthesis of 3,5,6-trichloropyridin-2-ol via the CuCl-catalyzed reaction of trichloroacetyl chloride and acrylonitrile under both pressure and atmospheric conditions and the hydrolysis of the reaction mixture were reinvestigated. The products and byproducts formed in each case, before the hydrolysis step, were char... | 10.1021/op025610t | 0 |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.