title string | abstract string | doi string | has_route int64 |
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Intelligent Electronic Laboratory Notebooks for Accelerated Organic Process R&D | Pharmaceutical companies are being forced to find methods to dramatically improve their research and development productivity and efficiency. One approach is replacing the paper laboratory notebooks that have been used in the same way for centuries with an electronic system. An intelligent electronic laboratory noteboo... | 10.1021/op049890j | 0 |
A Scaleable Synthesis of Fiduxosin | Fiduxosin ( 1 ) has been under development at Abbott Laboratories for the treatment of benign prostatic hyperplasia. A convergent strategy required methodologies for preparation of an enantiomerically pure 3,4- cis -disubstituted pyrrolidine and a 2,3,5-trisubstituted thienopyrazine in a regiospecific manner. A [3+2] c... | 10.1021/op049889k | 1 |
A New Process for Antineoplastic Agent Clofarabine | Clofarabine is a promising DNA polymerase inhibitor currently in clinical trials for a variety of liquid and solid tumor indications. The efforts for development of a new manufacturing process for clofarabine are presented. This new process allows for the reliable and efficient production of drug substance in high anom... | 10.1021/op049884n | 0 |
Scale-Up and Safety Evaluation of a Sandmeyer Reaction | A scale-up of a new process for the production of 2-chloro-5-trifluoromethyl-benzonitrile by a Sandmeyer reaction of 2-Chloro-5-trifluoromethylaniline with copper cyanide/sodium cyanide is described. To ensure a safe implementation, a safety evaluation of the process was carried out, which is described in the following... | 10.1021/op0498823 | 0 |
Green Engineering: Environmentally Conscious Design of Chemical Processes By David T. Allen and David R. Shonnard. Prentice Hall PTR: New Jersey. 2002. 552 pp. £51.99. ISBN 0-13-061908-6. | ADVERTISEMENT RETURN TO ISSUEPREVBook ReviewNEXTGreen Engineering: Environmentally Conscious Design of Chemical Processes By David T. Allen and David R. Shonnard. Prentice Hall PTR: New Jersey. 2002. 552 pp. £51.99. ISBN 0-13-061908-6.Peter L. SpargoView Author Information Scientific Update LLP, Maycroft Place, Stone C... | 10.1021/op049881a | 0 |
Facile and Practical Synthesis of 2,6-Dichloropurine | A facile and industrially viable process for preparation of 2,6-dichloropurine is reported. The process involves direct chlorination of xanthine with phosphorus oxychloride and a weak nucleophilic organic base, such as amidine, guanidine base, or Proton-Sponge. | 10.1021/op049878r | 0 |
Regioselective Synthesis of 1-Aklyl-4-(3-pyridyl)-Substituted Imidazole | A practical and regioselective synthesis of 1-alkyl-4-(3-pyridyl) imidazole via a Suzuki coupling reaction employing 3-pyridylboronates has been investigated. The use of sec -butyllithium in place of n -butyllithium for complete selectivity in removing bromines on tribromoimidazole to provide a key bromoimidazole coupl... | 10.1021/op0498767 | 0 |
High-Throughput Experimentation in Pharmaceutical Process R&D: Developing a New Software Workflow to Overcome Downstream Data-Analysis Bottlenecks and Improve Productivity | A new software workflow is described to overcome our data analysis, data-modification, and visualisation bottlenecks. Through a combination of in-house and external supplier expertise, a software workflow has been developed to tackle the mass of data generated from high-throughput experimentation. Also described is our... | 10.1021/op049873u | 0 |
A Novel and Efficient Route to Zafirlukast | Zafirlukast, an important drug for allergic pulmonary disorders such as asthma, is synthesized by a five-step, high-yielding, and inexpensive process. | 10.1021/op049869i | 1 |
An Improved Process for the Large-Scale Preparation of Antirheumatic Agent MX-68 | A large-scale preparation route of MX-68, a novel MTX derivative bearing a dihydro-2 H -1,4-benzothiazine moiety and l -homogulutamic acid, is described. The original route that is a laboratory-scale synthesis for preclinical study has been improved. The improved process involves the following features: each step does ... | 10.1021/op049867y | 1 |
Process R&D: Past and Present | ADVERTISEMENT RETURN TO ISSUEEditorialNEXTProcess R&D: Past and PresentTrevor LairdView Author Information Editor Cite this: Org. Proc. Res. Dev. 2004, 8, 5, 689Publication Date (Web):August 11, 2004Publication History Published online11 August 2004Published inissue 1 September 2004https://pubs.acs.org/doi/10.1021/op04... | 10.1021/op0498666 | 0 |
DioRaSSP: Diosynth Rapid Solution Synthesis of Peptides | We have developed a novel method for the large-scale manufacturing of peptides in solution called DioRaSSP. It combines the advantages of the homogeneous character of classical solution-phase synthesis with the generic character and the amenability to automation inherent to the solid-phase approach. DioRaSSP is charact... | 10.1021/op049864l | 0 |
Selective Synthesis of <i>p</i>-Hydroxybenzaldehyde by Liquid-Phase Catalytic Oxidation of <i>p</i>-Cresol | Liquid-phase oxidation of p -cresol over insoluble cobalt oxide (Co 3 O 4 ) catalyst under elevated pressure of air gave 95% selectivity to p -hydroxybenzaldehyde, an important flavoring intermediate. The selectivity to p -hydroxybenzaldehyde could be enhanced by manipulating the concentrations of p -cresol, sodium hyd... | 10.1021/op0498619 | 0 |
Acrylate as an Efficient Dimethylamine Trap for the Practical Synthesis of 1-<i>tert</i>-Butyl-4-piperidone via Transamination | Efficient trapping of dimethylamine was the key to success in the transamination of 1,1-dimethyl-4-oxopiperidinium iodide with tert -butylamine to afford 1- tert -butylpiperidin-4-one in high yield. The use of sodium acrylate was found to provide an elegant way to both trap dimethylamine and provide a convenient method... | 10.1021/op049860g | 1 |
Synthesis of Methyl Phenyl Glyoxylate via Clean Oxidation of Methyl Mandelate over a Nanocatalyst Based on Heteropolyacid Supported on Clay | Oxidation is an important class of reaction from both industrial and academic points of view. In recent years, a large number of oxidizing agents have been used for a variety of industrial reactions, but many of them are polluting, giving poor yields. Mandelates have played an important role in organic synthesis and ar... | 10.1021/op049858p | 0 |
Solid-Supported Continuous Flow Synthesis in Microreactors Using Electroosmotic Flow | This paper reports the fabrication of a microreactor suitable for use with supported reagents. We demonstrate that the electroosmotic flow can be used to move the reagents over a solid-supported catalyst bed. It is demonstrated that it is important that the support should not swell in organic solvents to obtain reprodu... | 10.1021/op049857x | 0 |
Scaleable Syntheses of Isomeric Limonene Aziridines from the Commercially Available Mixture of <i>cis</i>- and <i>trans</i>-Limonene Oxides | A short and efficient route to both isomers of limonene aziridine is described. The process is amenable to scale-up and allows easy access to multigram quantities of these highly useful chiral building blocks. | 10.1021/op0498464 | 0 |
Practical Process for the Air Oxidation of Cresols: Part A. Mechanistic Investigations | The catalytic air oxidation of p -cresol and 2,6-di- tert -butyl-4-methylphenol to the corresponding benzaldehydes was investigated to determine the mechanism at work in these oxidation reactions. A number of intermediates and byproducts, mainly in the form of dimers, were observed during the course of the reactions, a... | 10.1021/op049845b | 0 |
Practical Process for the Air Oxidation of Cresols: Part B. Evaluation of the Laboratory-Scale Oxidation Process | Mechanistic proposals and predictions made in a preceding paper (Part A) were evaluated by carrying out the catalytic air oxidation of p -cresol in an alternative solvent system, comprising either a mixture of ethylene glycol and acetic acid (for oxidations under acidic conditions) or ethylene glycol and water (for oxi... | 10.1021/op049844j | 0 |
Large Scale Deprotection of a <i>tert</i>-Butoxycarbonyl (Boc) Group Using Aqueous HCl and Acetone | A procedure for tert -butoxycarbonyl (Boc) group removal using concentrated HCl and acetone was developed and utilized on multi-kilogram scale in the synthesis of LY544344·HCl ( 1 ). The details surrounding this procedure and the advantages offered by it are described herein. | 10.1021/op049842z | 0 |
Chemical Process Research: The Art of Practical Synthesis Edited by Ahmed F. Abdel-Magid and John A. Ragan. ACS Symposium Series 870. American Chemical Society: Washington, DC. 2004. 211 pp. Price $125. ISBN 0-8412-3824-3. | ADVERTISEMENT RETURN TO ISSUEPREVBook ReviewNEXTChemical Process Research: The Art of Practical Synthesis Edited by Ahmed F. Abdel-Magid and John A. Ragan. ACS Symposium Series 870. American Chemical Society: Washington, DC. 2004. 211 pp. Price $125. ISBN 0-8412-3824-3.W. J. WatsonView Author Information Scientific Upd... | 10.1021/op049840e | 0 |
An Efficient Catalytic Asymmetric Route to 1-Aryl-2-imidazol-1-yl-ethanols | The asymmetric hydrogenation of 1-aryl-2-imidazol-1-yl-ethanones offers a concise route to homochiral 1-aryl-2-imidazol-1-yl-ethanols. Catalytic asymmetric transfer hydrogenation with formic acid using [( R, R )-TsDPEN]Ru(Cymene)Cl as precatalyst was shown to be effective in this transformation. Preliminary process dev... | 10.1021/op049838n | 0 |
Minimizing Isobutylene Emissions from Large Scale<i>tert</i>-Butoxycarbonyl Deprotections | Isobutylene off-gas amounts liberated during the methanesulfonic acid-catalyzed deprotection of N -BOC−pyrrolidine in THF, methanol, ethanol, 2-propanol, toluene, and dichloromethane were measured using on-line gas-phase mass spectroscopy. While one full equivalent of isobutylene was released as an off-gas when THF was... | 10.1021/op049837v | 0 |
An Expeditious Scalable Synthesis of (<i>S</i>)-2-Amino-5-methoxytetralin via Resolution | The first resolution of (±)-2-amino-5-methoxytetralin 1 is achieved via diastereomeric salt formation with ( S )-mandelic acid to give ( S )- 1 ·HCl of 99.7% ee in 29% overall yield from (±)- 1 ·HCl, ( S )- 1 ·HCl being a chiral intermediate to assemble N-0923 2, a potent dopamine D 2 agonist effective against Parkinso... | 10.1021/op0498363 | 1 |
An Efficient and Safe Procedure for the Large-Scale Pd-Catalyzed Hydrazonation of Aromatic Chlorides Using Buchwald Technology | A convenient, optimized and safe synthesis of N -arylhydrazines, useful as intermediates for active ingredients in agricultural and pharmaceutical applications, is reported. Starting from aryl halides (chlorides and bromides), a palladium-catalyzed carbon−nitrogen coupling reaction followed by an acidic treatment affor... | 10.1021/op049832y | 0 |
Process Development of (1<i>S</i>,2<i>S</i>,5<i>R</i>,6<i>S</i>)- Spiro[bicyclo[3.1.0]hexane-2‘,5‘-dioxo-2,4‘-imidazolidine]-6-carboxylic Acid, (<i>R</i>)-α-Methylbenzenemethanamine Salt (LSN344309) | Process development and a pilot-plant process for the synthesis of 4 and its resolution to obtain (1 S,2 S,5 R,6 S )-spiro[bicyclo[3.1.0]hexane-2‘,5‘-dioxo-2,4‘-imidazolidine]-6-carboxylic acid, ( R )-α-methylbenzenemethanamine salt ( 5 ) are described. Starting from the inexpensive raw 2-cyclopenten-1-one and sulfur y... | 10.1021/op049829e | 1 |
A Novel Eco-Friendly Process for the Synthesis of 2-Chlorobenzylidenemalononitrile and ITS Analogues Using Water As a Solvent | A simple and novel eco-friendly process for the synthesis of 2-chlorobenzylidene malononitrile (CS) and their analogues in water using 1-methyl imidazole (catalyst) has been developed. The reaction conditions for the preparation of CS are optimized for large scale applications. | 10.1021/op0498262 | 0 |
Industrial Synthesis of Maxacalcitol, the Antihyperparathyroidism and Antipsoriatic Vitamin D<sub>3</sub> Analogue Exhibiting Low Calcemic Activity | Maxacalcitol, the 22-oxa-derivative of 1α,25-dihydroxyvitamin D 3 and used currently as an antihyperparathyroidism and antipsoriatic drug, has been synthesized in seven chemical steps from 1α-hydroxydehydroepiandrosterone on the basis of our previously developed route. The present synthesis allows the production of the... | 10.1021/op049822x | 1 |
<i>SPECIAL FEATURE SECTION: <u>SOFTWARE FOR APPLICATION IN CHEMICAL DEVELOPMENT AND SCALE-UP</u></i> | ADVERTISEMENT RETURN TO ISSUEPREVEditorialNEXTSPECIAL FEATURE SECTION: SOFTWARE FOR APPLICATION IN CHEMICAL DEVELOPMENT AND SCALE-UPDavid LathburyView Author Information AstraZeneca R&D Charnwood, Bakewell Road, Loughborough, Leicestershire LE11 5RH, UK Cite this: Org. Proc. Res. Dev. 2004, 8, 6, 964Publication Date (W... | 10.1021/op0498215 | 0 |
Chemical Micro Process Engineering: Fundamentals, Modelling and Reactions, 10th ed by V. Hessel, S. Hardt, and H. Löwe. Kluwer Academic Publishers: Dordrecht. 2003. Wiley-VCH: Weinheim. 2004. xxxviii + 674 pp. £135. ISBN 3-527-30741-9. | ADVERTISEMENT RETURN TO ISSUEPREVBook ReviewNEXTChemical Micro Process Engineering: Fundamentals, Modelling and Reactions, 10th ed by V. Hessel, S. Hardt, and H. Löwe. Kluwer Academic Publishers: Dordrecht. 2003. Wiley-VCH: Weinheim. 2004. xxxviii + 674 pp. £135. ISBN 3-527-30741-9.Cite this: Org. Process Res. Dev. 200... | 10.1021/op0498161 | 0 |
Development of a Scalable Process for 1-(3,5-Dichlorophenyl)-5-iodo-3-methyl- (4-methylbenzyl)-1<i>H</i>-imidazo[1,2-<i>a</i>]imidazol-2-one: A Key Intermediate for the Synthesis of LFA-1 Inhibitors | A safe, robust, chromatography-free and reproducible process for the multi-kilogram synthesis of vinyl iodide 2, a key intermediate for the synthesis of LFA-1 inhibitors, was developed and implemented at the pilot plant. Execution of the above process allowed us to support preclinical activities in the LFA-1 program. | 10.1021/op049813o | 0 |
Process Development and Scale-up of a Selective α<sub>1</sub>-Adrenoceptor Antagonist | A synthetic route to a potent and selective α-1-adrenergic receptor antagonist has been developed and demonstrated in a pilot plant. The route has been used in two pilot plant campaigns and has produced RO3203546 in 2.3 and 12.0 kg batch sizes. The first pilot plant campaign focused primarily on the end-game of the pro... | 10.1021/op0498114 | 1 |
A Facile and Scaleable Synthesis of ABT-239, A Benzofuranoid H<sub>3</sub> Antagonist | A facile and scaleable synthesis of a potent and selective histamine H 3 receptor antagonist, ABT-239 ( 1 ), was developed starting from commercially available 4‘-hydroxy-biphenyl-4-carbonitrile ( 2 ). The synthesis comprised four chemical steps and a salt formation step with an overall yield of 40%. A highly selective... | 10.1021/op049809c | 1 |
Investigation of Practical Routes for the Kilogram-Scale Production of <i>cis</i>-3-Methylamino-4-methylpiperidines | Two routes for the synthesis of cis - N -protected-3-methylamino-4-methylpiperidine ( 3 ) were examined: a route hinging on the electrochemical oxidation of carbamate 1 to install a ketone at the 3 position of the piperidine followed by reductive amination (disconnection A), and a route involving the hydrogenation of a... | 10.1021/op049808k | 1 |
A Formal Synthesis of (+)-Discodermolide | Herein, we report the formal synthesis of (+)-discodermolide ( 1 ), a promising anticancer agent of sponge origin, in 24 linear steps, with 35 steps in total. The route proceeds from lactone 2, a building block containing the common 1,2- anti -2,3 -syn stereotriad found in each of the three subunits, methyl ketone 4 (C... | 10.1021/op049807s | 1 |
Practical Synthesis of Triethylammonium (<i>Z</i>)-2-[2-(Boc-amino)thiazol-4-yl]-2-(trityloxyimino)acetate, the Side Chain of Cefmatilen | A practical synthesis of triethylammonium ( Z )-2-[2-( N - tert -butoxycarbonylamino)thiazol-4-yl]-2-(triphenylmethyloxyimino)acetate ( 1 ) which is the C-7 side chain of cefmatilen, a new cephalosporin antibiotic, is described. The conditions were optimized to control the impurity and to increase the yield. Selective ... | 10.1021/op049804f | 1 |
Profiling the Formation of 2-Chloro-<i>N,N</i>-dimethylamino Trimethinium Chloride Salt, a Key Intermediate in the Manufacturing Process of Etoricoxib | 2-Chloro- N, N -dimethylamino trimethinium chloride salt (CDT-chloride) is a key intermediate in the synthesis of Etoricoxib, a selective COX-2 inhibitor developed by Merck & Co., Inc. The formation of CDT-chloride from a mixture of chloroacetic acid and POCl 3 in DMF was monitored by in situ IR and in situ NIR. The bu... | 10.1021/op049802v | 0 |
Determination of the Source of the <i>N</i>-Methyl Impurity in the Synthesis of Pemetrexed Disodium Heptahydrate | The synthesis of Pemetrexed Disodium Heptahydrate has consistently resulted in a very low level (ca. 0.02%) unknown impurity. To ensure long-term control, the identity and source of the impurity were desired. Isolation and characterization identified the impurity as the N -methyl derivative. The source was identified a... | 10.1021/op0498013 | 1 |
A Study of the Paterson Boron Aldol Reaction as Used in the Large-Scale Total Synthesis of the Anticancer Marine Natural Product (+)-Discodermolide | This note discusses an optimisation study of a key reagent-controlled enantioselective boron enolate aldol reaction forming the C 6 −C 7 bond and the C 7 hydroxyl-bearing stereocenter in (+)-discodermolide. Conditions were found which increased the yield, decreased the excess of enolate necessary, and increased product... | 10.1021/op049800a | 1 |
Chemistry Development of a Convergent Route to Trecetilide Hemi-Fumarate | A novel, efficient, stereoselective synthetic route for N -(4-{4-[ethyl(6-fluoro-6-methylheptyl)amino]-1-( S )-hydroxybutyl}phenyl)methanesulfonamide hemi-fumaric acid salt (trecetilide hemi-fumarate, Figure 1) has been developed. The process features a convergent approach, which assembles two key intermediates in the ... | 10.1021/op049799f | 1 |
The Chemistry of Process Development in Fine Chemical & Pharmaceutical Industry By C. Someswara Rao. Asian Books Private Limited: New Delhi. 2004. 1277 pp. ISBN 81-86299-50-5. | ADVERTISEMENT RETURN TO ISSUEPREVBook ReviewThe Chemistry of Process Development in Fine Chemical & Pharmaceutical Industry By C. Someswara Rao. Asian Books Private Limited: New Delhi. 2004. 1277 pp. ISBN 81-86299-50-5.Cite this: Org. Process Res. Dev. 2005, 9, 1, 123Publication Date (Web):December 24, 2004Publication ... | 10.1021/op049792y | 0 |
Practical Synthesis of an Orally Active CCR5 Antagonist, 7-{4-[2-(Butoxy)- ethoxy]phenyl}-<i>N</i>-(4-{[methyl(tetrahydro-2<i>H</i>-pyran-4-yl)amino]methyl}phenyl)- 1-propyl-2,3-dihydro-1<i>H</i>-1-benzazepine-4-carboxamide | A practical method of synthesizing 7-{4-[2-(butoxy)ethoxy]phenyl}- N -(4-{[methyl(tetrahydro-2 H -pyran-4-yl)amino]methyl}phenyl)-1-propyl-2,3-dihydro-1 H -1-benzazepine-4-carboxamide ( 8 ), an orally active CCR5 antagonist, has been developed. Methyl 7-bromo-1-propyl-2,3-dihydro-1 H -1-benzazepine-4-caboxylate ( 14a )... | 10.1021/op0497916 | 1 |
A New Purification Process for Pharmaceutical and Chemical Industries | A novel separation and purification process suitable for pharmaceutical and chemical industries has been developed. The process is based on the difference in adsorption and solubility of organic compounds. The process was carried out under mechanical stirring, and individual components were isolated in short time with ... | 10.1021/op049790d | 0 |
Improvement of Dye Properties of the Azo Pigment Yellow 12 Using a Micromixer-Based Process | The properties of coloured pigments are primarily affected by the particle size as well as the size distribution. As both are influenced by the production process, the pigment synthesis of Yellow 12 was investigated using a micromixer apparatus. The micromixer ensures fast mixing by multilamination of thin lamellae and... | 10.1021/op049789e | 0 |
Development of the One-Carbon Homologation of a 4-Methylcoumarin Assisted by In-Line FTIR | In-line FTIR was applied as a suitable PAT (process analytical technology) to monitor and control the enolate formation step in the one-carbon homologation process of a 4-methylcoumarin with chloromethyl pivalate. The techniques to determine the endpoint of the reaction and to obtain kinetic and stability data both in ... | 10.1021/op049787u | 0 |
Practical Synthesis of FR195752, the Side Chain of Micafungin, Utilizing a Regioselective Conversion of Diaryl-β-diketone to 3,5-Diarylisoxazole | The practical synthesis of FR195752, the side chain of Micafungin, was established utilizing a highly regioselective conversion of diaryl-β-diketone to 3,5-diarylisoxazole via the corresponding β-keto enamine intermediate whose disfavored regioisomer could be recycled efficiently after its hydrolysis. In addition, the ... | 10.1021/op0497862 | 1 |
Straightforward Preparation of Highly Enantioselective Anchored Chiral Homogeneous Catalysts | A new method of anchoring homogeneous catalysts onto basic carbons is presented. The ease of the preparation is particularly remarkable, and the method proved to be suitable for scale-up. In the case of asymmetric heterogeneous catalysts for hydrogenation reactions, enantioselective improvement was observed in all case... | 10.1021/op049785+ | 0 |
A Review of the Use of Process Analytical Technology for the Understanding and Optimization of Production Batch Crystallization Processes | Crystallization at production scale is typically a poorly understood unit operation, with little implementation of the first principles aspect of crystallization in its design, optimization, and control. Problems with production crystallizers include the following: (1) inconsistencies of batch-to-batch in terms of the ... | 10.1021/op049783p | 0 |
Selectivity Control by Use of Near-IR for a Hydrogenation Process | We applied process analytical technologies to solve the problem of selectivity in the hydrogenation of 3-(2-chloroethyl)-9-hydroxy-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one monohydrochloride ( 1 ) to (±)3-(2-chloroethyl)-6,7,8,9-tetrahydro-9-hydroxy-2-methyl-4H-pyrido[1,2- a ]pyrimidin-4-one monohydrochloride ( 2 ). We ... | 10.1021/op049782x | 0 |
An Efficient Commercial Process for the Preparation of Isotretinoin | We describe an efficient process for the preparation of isotretinoin (13-cis isomer of vitamin A acid) in a single step starting from β-ionylidene acetaldehyde ( 5 ). The process conditions are convenient to operate on a commercial scale and afford isotretinoin of excellent quality; levels of related isomeric impuritie... | 10.1021/op0497815 | 1 |
Preparation of Optically Pure Esomeprazole and Its Related Salt | The magnesium salt of ( S )-isomer of omeprazole, with a trade name of Nexium, is the first proton-pump inhibitor developed as a single isomer for the treatment of acid-related diseases. A process for the preparation of the optically pure ( S )-isomer of omeprazole through transition metal complex is described. | 10.1021/op049779d | 1 |
Scale-Up of a Reformatsky Reaction to an Indenyl Butanoate | A safe process for the Reformatsky reaction of 5-methoxy-1-indanone and methyl 2-bromo butyrate giving an indenyl butanoate was developed. It was scaled-up from the lab to the pilot plant. The results from two campaigns on pilot-plant scale are presented. | 10.1021/op049778l | 0 |
An Improved Large Scale Synthesis of the Schöllkopf Chiral Auxiliaries: (2<i>R</i>)- and (2<i>S</i>)<i>-</i>2,5-Dihydro-3,6-dimethoxy-2-isopropylpyrazine | Syntheses of the Schöllkopf chiral auxiliaries have been carried out on large scale in high overall yields from d - and l -valine. This method avoids the use of highly toxic phosgene or triphosgene, low-temperature reactions, and unstable intermediates. | 10.1021/op049777t | 1 |
A Practical and One-Pot Procedure for the Synthesis of 3-Amino-2-cyclohexen-1-one from 3-Aminophenol | A simple, totally catalytic, and environmentally benign process for the synthesis of 3-amino-2-cyclohexen-1-one using 10% Pd/C-catalyzed hydrogenation has been developed. | 10.1021/op0497761 | 0 |
A Practical Large-Scale Synthesis of (3<i>R</i>,4<i>R</i>)-4-(Hydroxymethyl)pyrrolidin-3-ol via Asymmetric 1,3-Dipolar Cycloaddition | (3 R,4 R )-4-(Hydroxymethyl)pyrrolidin-3-ol ( 1 ), which is a useful intermediate for the synthesis of various bioactive molecules, has been synthesized in 51% overall yield by 1,3-dipolar cycloaddition reaction from the dipolarophile, ( E )-3-benzyloxypropenoyl-(2‘ S )-bornane-10,2-sultam ( 5 ), and the achiral ylide ... | 10.1021/op049768k | 1 |
Adsorbent Screening for Metal Impurity Removal in Pharmaceutical Process Research | A microtube screening approach affords simple and convenient assessment of the selective adsorption of metal impurities by a variety of different process adsorbents. This approach is helpful in identifying rapid solutions to metal impurity problems in pharmaceutical process research. Several examples illustrating the u... | 10.1021/op049764f | 0 |
A New Industrial Process for Oxcarbazepine | A novel industrial process for the antiepileptic drug oxcarbazepine 1 has been developed. Unlike the old process, the new process is free from halogenated solvents and can be performed in standard production equipment. It starts from commercially available 1,3-dihydro-1-phenyl-2H-indol-2-one 10 . In the key step, an el... | 10.1021/op049760a | 1 |
Process Analytical Technology: An Investment in Process Knowledge | Process analytical technology (PAT) is fast becoming an integral part of many active pharmaceutical ingredient (API) production facilities. The incorporation of early PAT devices, such as pH probes for example, was shown to increase process efficiency and safety by acting on data in real time and by eliminating samplin... | 10.1021/op0402127 | 0 |
Viral Clearance Issues Associated with the Use of an Animal-Derived Enzyme in the Synthesis of Emtricitabine | Emtricitabine, the active ingredient in the antiviral drug Coviracil, has been prepared by a process using pig liver esterase to resolve optical isomers of an intermediate. Since this enzyme was derived from an animal source, potential existed for viral contamination of the product and the multipurpose equipment in whi... | 10.1021/op040210m | 0 |
Reply to Comment on “Optimisation of the Linear Alkyl Benzene Sulfonation Process for Surfactant Manufacture” and “Sulfonation Technology for Anionic Surfactant Manufacture”: Falling Film SO<sub>3</sub> Sulfonation - Laminar or Turbulent Flow Controversy | ADVERTISEMENT RETURN TO ISSUEPREVCommunication to Edi...Communication to EditorNEXTReply to Comment on “Optimisation of the Linear Alkyl Benzene Sulfonation Process for Surfactant Manufacture” and “Sulfonation Technology for Anionic Surfactant Manufacture”: Falling Film SO3 Sulfonation - Laminar or Turbulent Flow Contr... | 10.1021/op040209n | 0 |
Comment on “Optimisation of the Linear Alkyl Benzene Sulfonation Process for Surfactant Manufacture” and “Sulfonation Technology for Anionic Surfactant Manufacture”: Falling Film SO<sub>3</sub> Sulfonation - Laminar or Turbulent Flow Controversy | ADVERTISEMENT RETURN TO ISSUEPREVCommunication to Edi...Communication to EditorNEXTComment on "Optimisation of the Linear Alkyl Benzene Sulfonation Process for Surfactant Manufacture" and "Sulfonation Technology for Anionic Surfactant Manufacture": Falling Film SO3 Sulfonation - Laminar or Turbulent Flow ControversyEdw... | 10.1021/op0402073 | 0 |
Use of DOE for Rapid Development of a Red-Al Reduction Process for the Synthesis of 3,4-Isopropylidenedioxypyrrolidine Hydrotosylate | Statistical design of experiments (DOE) was used to rapidly optimize Red-Al reduction of an imide to produce, after deprotection and salt formation, 3,4-isopropylidenedioxypyrrolidine hydrotosylate ( 1 ), an intermediate in the synthesis of Ingliforib. A Red-Al reduction process was successfully scaled to produce multi... | 10.1021/op040204q | 1 |
Development of an Efficient Process for the Preparation of Sch 39166: Aziridinium Chemistry on Scale | A large-scale synthesis of a tricyclic D1/D5 dopamine antagonist based on regio- and stereoselective ring opening of an aziridinium ion with a Grignard reagent was optimized and scaled up. | 10.1021/op0402026 | 1 |
Canonical Analysis of Response Surfaces: A Valuable Tool for Process Development<sup>1</sup> | The principles of response surface modelling are briefly described. The computations involved in the canonical analysis of response surface models are given in detail. Three examples of canonical analysis in the context of organic synthesis development are discussed. These examples treat enamine synthesis by a modified... | 10.1021/op040023o | 0 |
Synthesis of Commercial Phosphodiesterase(V) Inhibitors | The literature syntheses (including patents) of three commercial phosphodiesterase(V) (PDE5) inhibitors (sildenafil, vardenafil, and tadalafil) are reviewed with particular emphasis on large-scale manufacture. For each of these compounds, some impressive chemical development work has been reported. | 10.1021/op040019c | 1 |
Synthetic Process Development and Scale-Up of the Oxidative Cleavage of a Double Bond Catalyzed by Ruthenium Trichloride | Using statistical experimental tools, a relatively complex process for the oxidative cleavage of a double bond catalyzed by a ruthenium catalyst was studied. A good understanding of the influence of the reaction parameters led to the development of a technically feasible process which was successively scaled up to kilo... | 10.1021/op040014f | 0 |
Application of Process Modelling Tools in the Scale-Up of Pharmaceutical Crystallisation Processes | Crystallisations are frequent process steps in the manufacture of active pharmaceutical ingredients (APIs). They are the primary means of intermediate or product formation and separation to achieve the desired purity and form. These unit operations are complex processes which are difficult to control due to the interli... | 10.1021/op040013n | 0 |
Sanofi-Synthelabo Chemical Development and the Development of an Electronic Laboratory Notebook | Past attempts to develop electronic laboratory notebooks (ELN) have not always met with the success expected of them. This may have been due to job aspects and the difficulties encountered in their practical application, insufficient support provided to users during the learning phase, application complexity, interfaci... | 10.1021/op040012v | 0 |
Synthesis of Trifluoromethanesulfonic Acid from CHF<sub>3</sub> | Trifluoromethane is transformed to trifluoromethanesulfonic acid (TFMSA) at low temperature in a liquid-phase reaction in a strong acid such as fuming sulfuric acid as well as in a strong basic solution such as t -BuOK/DMF. | 10.1021/op040007r | 0 |
Claisen Condensation as a Facile Route to an α-Alkoxy-cinnamate: Synthesis of Ethyl (2<i>S</i>)-2-Ethoxy-3-(4-hydroxyphenyl)propanoate | The title compound was prepared from p -anisaldehyde and ethyl ethoxyacetate via a racemic synthetic route. The synthesis involves a Claisen-type condensation in which the elimination was unexpectedly promoted by an excess of the ester. The process has been successfully performed on a 2000-L scale with a total yield ov... | 10.1021/op040006z | 1 |
An Improved Process for the Preparation of Trimethylhydrazine and Its Coupling with an Activated Acid Intermediate | Trimethylhydrazine (TMH) was prepared in two steps from 1,1-dimethylhydrazine, using an easy to scale-up procedure that avoided difficult acid−base extractions. The procedure provided TMH as a solution in 1,4-dioxane, in a form that was easy and safe to handle in a coupling with an enantiomerically pure, sterically hin... | 10.1021/op0342022 | 1 |
<i> SPECIAL FEATURE SECTION: <u>SAFETY OF CHEMICAL PROCESSES</u> </i> Are MSDs Safe? Reflections at the MSDS's 20th Birthday <sup>1</sup> | ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSPECIAL FEATURE SECTION: SAFETY OF CHEMICAL PROCESSES Are MSDs Safe? Reflections at the MSDS's 20th Birthday1Giora AgamView Author Information Pi2Chim Ltd., Consultation Services in Chemical and Biotechnological R&D, Beer-Sheva, Israel E-mail: [email protected]Cite this: Org.... | 10.1021/op034201+ | 0 |
Continuous Microflow Synthesis of Butyl Cinnamate by a Mizoroki−Heck Reaction Using a Low-Viscosity Ionic Liquid as the Recycling Reaction Medium | A continuous microflow system was developed with efficient catalyst recycling for a Mizoroki−Heck reaction of iodobenzene with butyl acrylate, using a low-viscosity ionic liquid ([bmim]NTf 2 ) as the reaction medium. Using a CPC CYTOS Lab System as the microreaction apparatus, in combination with an originally develope... | 10.1021/op034200h | 0 |
Re-engineering the Chemical Processing Plant: Process Intensification Edited by Andrzej Stankiewicz and Jacob A. Moulijn. Marcel Dekker: New York. 2004. $165. 529 pp. ISBN 0-8247-4302-4. | ADVERTISEMENT RETURN TO ISSUEPREVBook ReviewNEXTRe-engineering the Chemical Processing Plant: Process Intensification Edited by Andrzej Stankiewicz and Jacob A. Moulijn. Marcel Dekker: New York. 2004. $165. 529 pp. ISBN 0-8247-4302-4.Cite this: Org. Proc. Res. Dev. 2004, 8, 2, 299Publication Date (Web):January 28, 2004... | 10.1021/op034199m | 0 |
A Practical Synthesis of a Potent δ-Opioid Antagonist: Use of a Modified Knorr Pyrrole Synthesis | A modified Knorr pyrrole reaction is described which may have practical benefits for the large-scale synthesis of SB-342219. The use of zinc to reduce a phenylhydrazone is replaced by the hydrogenation of the corresponding oxime to provide a common aminoketone intermediate. The modifications have practical benefit with... | 10.1021/op034198u | 0 |
Asymmetric Catalysis on Industrial Scale: Challenges, Approaches and Solutions Edited by H. U. Blaser and E. Schmidt. Wiley-VCH: Weinheim. 2004. £115. 454 pp. ISBN 3-527-30631-5. | null | 10.1021/op034196+ | 0 |
Microwaves in Organic Synthesis Edited by Andre Loupy. Wiley-VCH: Weinheim. 2002. 159 euro. 499 pp. ISBN 3-527-30514-9. | ADVERTISEMENT RETURN TO ISSUEPREVBook ReviewNEXTMicrowaves in Organic Synthesis Edited by Andre Loupy. Wiley-VCH: Weinheim. 2002. 159 euro. 499 pp. ISBN 3-527-30514-9.Peter SpargoView Author Information Scientific Update LLP, Maycroft Place, Stone Cross, Mayfield, East Sussex, TN20 6EW, UKCite this: Org. Proc. Res. Dev... | 10.1021/op034195h | 0 |
Application of Microreactor Technology in Process Development | The microreactor technology is an efficient tool for kilogram-scale syntheses in continuous mode and is particularly effective for hazardous reactions that do not allow scale-up in conventional reactors. Applications to several classes of reactions including highly exothermic reactions, high-temperature reactions, reac... | 10.1021/op034193x | 0 |
Example of Finishing Technologies as Key Elements for Successful Active Pharmaceutical Ingredient Process Development | Little has been published so far to emphasize the role of finishing technologies (crystallization, filtration, drying) as crucial elements for successful process development of active pharmaceutical ingredients (APIs). In the presented example high marketing forecasts stressed the objective for the process to be robust... | 10.1021/op034188t | 0 |
Process Development on an Efficient New Convergent Formal Synthesis of MIV-150 | Starting from a known linear route and a proposed convergent route, we have successfully developed a new hybrid convergent route to MIV-150 that takes advantage of the robust chemistry for the preparation of a fluoroketal and the stereospecific Negishi coupling of an iodocyclopropane moiety to a benzene ring. Stereosel... | 10.1021/op0341871 | 1 |
Process Development of a Scaleable Route to (2<i>R</i>)-[3-(2-Aminopropyl)-1<i>H</i>-indol-7-yloxy]-<i>N,N</i>-diethylacetamide: A Key Intermediate for AJ-9677, a Potent and Selective Human and Rat β<sub>3</sub>-Adrenergic Receptor Agonist | (2 R )-[3-(2-Aminopropyl)-1 H -indol-7-yloxy]acetic acid ( 2 ) is the left-hand side segment of AJ-9677, which is a potent and selective human and rat β 3 -adrenergic receptor agonist. Herein, we describe the process development of a scaleable synthetic route to the corresponding N,N -diethylacetamide derivative 3 of 2... | 10.1021/op0341869 | 1 |
Process Development of a Large-Scale Synthesis of TKA731: A Tachykinin Receptor Antagonist | An efficient and chromatography-free large-scale synthesis of a tachykinin receptor antagonist TKA731 ( 1 ), utilizing the coupling of dipeptide 7 and 2-chloro-4( 3H )-quinazolinone ( 13 ) as the key step, is described. The overall yield of 1 from BOC- l -3-(2-naphthyl)alanine ( 2 ) in six linear steps (total of eight ... | 10.1021/op0341824 | 1 |
Development and Applications of a Practical Continuous Flow Microwave Cell | A series of synthetic transformations were successfully and safely scaled up to multigram quantities using focused microwave irradiation with a continuous flow reaction cell that was developed in-house and which can be easily adapted to commercially available instrumentation. The representative reactions that were inve... | 10.1021/op034181b | 0 |
Development of a Practical Multikilogram Production of (<i>R</i>)-Seudenol by Enzymatic Resolution | Different enzymatic routes for the production of ( R )-seudenol were investigated. The Novozym 435-catalyzed reaction of racemic seudenol with vinyl butyrate proved to be the most promising route. By using vinyl laurate as an acyl donor, ( R )-seudenol laurate could be separated from ( S )-seudenol by an extractive wor... | 10.1021/op034179k | 0 |
Selectivity Gains and Energy Savings for the Industrial Phenyl Boronic Acid Process Using Micromixer/Tubular Reactors | An industrial production-scale process currently conducted at Clariant site/Frankfurt, termed Phenyl Boronic Acid Process from here on, was investigated at laboratory-scale using two micromixer/tubular reactor configurations, being equipped with either a glass interdigital (for details see (1) Ehrfeld, W.; Golbig, K.; ... | 10.1021/op0341768 | 0 |
A Simple Procedure for the Isolation of γ-Oxobenzenebutanoic Acid Derivatives: Application to the Synthesis of Fenbufen | A simple, convenient, and industrially viable process for the isolation of 4-oxobutanoic acid derivatives resulting from Friedel−Crafts acylation products of aromatic hydrocarbons with succinic anhydride is reported. The isolation procedure involves simple quenching of the reaction mixture followed by filtration of the... | 10.1021/op034173v | 0 |
Accelerated Process Development of Pharmaceuticals: Selective Catalytic Hydrogenations of Nitro Compounds Containing Other Functionalities | The hydrogenation of three different pharmaceutical nitro-containing compounds has been studied using high-throughput experimentation (HTE) methods. Significant improvements to the existing reactions were obtained for two of the examples. Each reaction exhibits distinct features regarding activity and chemoselectivity.... | 10.1021/op0341667 | 0 |
Assessing the Benefits of Direct Isolation Processes | Direct isolation processes are often used in pilot-plant and manufacturing operations. The primary benefit of a direct isolation process over a process using a conventional extractive workup and crystallization is the decreased cost of goods (COG) due to decreased processing time. Direct isolation processes may be bene... | 10.1021/op034165e | 0 |
Industrial Synthesis of 4-Chloro,11β-arylestradiol: How to Circumvent a Poor Diastereoselectivity | An industrial synthesis of 11β-arylestrone derivatives is described, based on the conjugate opening of a mixture of allylic 5(10)-α and -β epoxides by an aryl cuprate generated catalytically, followed by hydrolysis and subsequent aromatisation of the isomeric mixture of arylation products. An original method for select... | 10.1021/op0341622 | 1 |
Efficient Synthesis of Pyropheophorbide-<i>a</i> and Its Derivatives | A new and simplified method of preparing hexyloxy pyropheophorbide- a (HPPH), a promising agent used in photodynamic therapy, is described. This method is carried out in two processing steps, replacing an older method requiring five steps. This is accomplished by means of a Dieckmann condensation and subsequent thermal... | 10.1021/op034160h | 1 |
An Improved and Single-Pot Process for the Production of Pantoprazole Substantially Free from Sulfone Impurity | Pantoprazole ( 1 ), a substituted benzimidazole derivative, is an irreversible proton pump inhibitor, essentially used for the prevention and treatment of gastric acid-related diseases. The process for its preparation generally suffers from the drawback of producing a potential sulfone impurity ( 5 ). The present work ... | 10.1021/op034157y | 0 |
Organic Synthesis Highlights V Edited by Hans-Günther Schmalz and Thomas Wirth. Wiley VCH: Weinheim. 2003. 440 pp. £55. ISBN 3-527-30611-0. | ADVERTISEMENT RETURN TO ISSUEPREVBook ReviewNEXTOrganic Synthesis Highlights V Edited by Hans-Günther Schmalz and Thomas Wirth. Wiley VCH: Weinheim. 2003. 440 pp. £55. ISBN 3-527-30611-0.Cite this: Org. Proc. Res. Dev. 2004, 8, 2, 294–295Publication Date (Web):November 20, 2003Publication History Published online20 Nov... | 10.1021/op0341566 | 0 |
A Novel Process of Autoxidation of Cyclohexane Using Pure Oxygen | Autoxidation of liquid cyclohexane utilizing pure oxygen to produce cyclohexanone, cyclohexanol, and their precursors is achieved in a medium of cyclohexane/water mixture. The addition of water, which acts as an inert component, permits the use of pure oxygen without forming the potentially explosive oxygen/cyclohexane... | 10.1021/op0341521 | 0 |
A New and Simplified Process for Preparing <i>N</i>-[4-(3,4-Dichlorophenyl)-3,4-dihydro-1(2H)-naphthalenylidene]methanamine and a Telescoped Process for the Synthesis of (1<i>S</i>-<i>cis</i>)-4-(3,4-Dichlorophenol)-1,2,3,4-tetrahydro-<i>N</i>-methyl-1-naphthalenamine Mandelate: Key Intermediates in the Synthesis of S... | N -[4-(3,4-Dichlorophenyl)-3,4-dihydro-1(2H)-naphthalenylidene]methanamine, sertraline imine ( 3 ), is an intermediate for the synthesis of Zoloft, sertraline hydrochloride ( 1 ). A cleaner, simpler, and more efficient alternative to the Schiff base-mediated formation of sertraline imine has been developed and is prese... | 10.1021/op0341465 | 1 |
Development of a Scaleable Synthesis of a 3-Aminopyrazinone Acetamide Thrombin Inhibitor | A scaleable route to 2-{3-[(2,2-difluoro-2-(2-pyridyl)ethyl)amino]-6-chloro-2-oxohydropyrazinyl}- N -[(3-fluoro(2-pyridyl))methyl]acetamide 1 is described in which various scaleup issues were addressed to provide a safe, efficient, and robust route for the preparation of multi-kilo amounts of the compound. The use of e... | 10.1021/op0341420 | 1 |
<i>SPECIAL FEATURE SECTION: <u>SAFETY OF CHEMICAL PROCESSES</u></i> | ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSPECIAL FEATURE SECTION: SAFETY OF CHEMICAL PROCESSESTrevor LairdView Author Information Editor Cite this: Org. Proc. Res. Dev. 2003, 7, 6, 1028Publication Date (Web):October 11, 2003Publication History Published online11 October 2003Published inissue 1 November 2003https://p... | 10.1021/op034138o | 0 |
Solvent and Temperature Effects in the Free Radical Aerobic Oxidation of Alkyl and Acyl Aromatics Catalysed by Transition Metal Salts and <i>N</i>-Hydroxyphthalimide: New Processes for the Synthesis of <i>p</i>-Hydroxybenzoic Acid, Diphenols, and Dienes for Liquid Crystals and Cross-Linked Polymers | The aerobic oxidation of 4,4‘-diisopropyldiphenyl and 2,6-diisopropylnaphthalene, catalysed by N -hydroxyphthalimide and Co(II) salts, leads to the corresponding tertiary benzyl alcohols with high conversion and selectivity under mild conditions (temperature 30−60 °C and atmospheric pressure). Solvent and temperature e... | 10.1021/op034137w | 0 |
Large-Scale Synthesis of the Anti-Cancer Marine Natural Product (+)-Discodermolide. Part 5: Linkage of Fragments C<sub>1</sub><sub>-</sub><sub>6</sub> and C<sub>7</sub><sub>-</sub><sub>24</sub> and Finale | The finale of the large-scale preparation of 60 g of the highly complex marine natural product, (+)-discodermolide ( 1 ), using a hybridized Novartis−Smith−Paterson synthetic route is presented. This contribution, which is the concluding part of a five-part series, highlights a reagent-controlled stereoselective boron ... | 10.1021/op034134j | 1 |
Large-Scale Synthesis of the Anti-Cancer Marine Natural Product (+)-Discodermolide. Part 4: Preparation of Fragment C<sub>7</sub><sub>-</sub><sub>24</sub> | Coupling of C 9 - 14 ( 4 ) and C 15 - 21 ( 5a ) fragments to produce the cis -trisubstituted olefin was achieved using Suzuki-type coupling conditions employed by Marshall ( 5a / tert -BuLi/B-OMe-9-BBN added to 4 /Cs 2 CO 3 /Pd(dppf) 2 ). The terminal ( Z )-diene moiety was attached to aldehyde 10 by using a sequential... | 10.1021/op034133r | 1 |
Large-Scale Synthesis of the Anti-Cancer Marine Natural Product (+)-Discodermolide. Part 3: Synthesis of Fragment C<sub>15</sub><sub>-</sub><sub>21</sub> | Smith's procedure of preparing fragment C 15 - 21 ( 5 ) from common precursor 3 was optimized. The ease of plant operations made this six-step route successful for the production of several kilograms of this fragment with high purity. | 10.1021/op034132z | 1 |
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