- An efficient and stereoselective synthesis of (3S,4R)-(-)-trans-4- (4′-fluorophenyl)-3-hydroxymethyl-N-methylpiperidine
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An asymmetric conjugate addition reaction between a chiral α,β-unsaturated amido ester and ethyl-N-methylmalonamide has been used as a key step in the synthesis of (3S,4R)-(-)-trans-4-(4′- fluorophenyl)-3-hydroxymethyl-N-methylpiperidine, a key intermediate for (-)-paroxetine.
- Somaiah, Sripathi,Sashikanth, Suthrapu,Raju, Veeramalla,Reddy, Karnati Venugopal
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- AN IMPROVED PROCESS FOR THE PREPARATION OF PAROXETINE AND ITS INTERMEDIATE
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The present invention provides an improved process for the preparation of N-protected ((3S,4R)- 4-(4-fluorophenyl)piperidin-3-yl)methanol (compound (A)) and further its transformation to Paroxetine and its pharmaceutically acceptable salts. The process comprises reaction of compound (II) with amido-malonate compound (C) in the presence of a chiral catalyst and optionally a dehydrating agent to obtain compound (B); followed by reduction of (B) in the presence of a reducing agent to provide compound (A).
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(2017/03/21)
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- Substituted phenylpiperidines with serotoninergic activity and enhanced therapeutic properties
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Chemical syntheses and medical uses of novel inhibitors of the uptake of monoamine neurotransmitters and pharmaceutically acceptable salts and prodrugs thereof, for the treatment and/or management of psychotropic disorders, anxiety disorder, generalized anxiety disorder, depression, post-traumatic stress disorder, obsessive-compulsive disorder, panic disorder, hot flashes, senile dementia, migraine, hepatopulmonary syndrome, chronic pain, nociceptive pain, neuropathic pain, painful diabetic retinopathy, bipolar depression, obstructive sleep apnea, psychiatric disorders, premenstrual dysphoric disorder, social phobia, social anxiety disorder, urinary incontinence, anorexia, bulimia nervosa, obesity, ischemia, head injury, calcium overload in brain cells, drug dependence, and/or premature ejaculation are described. [image]
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(2010/11/27)
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- ENANTIOSPECIFIC PROCESS FOR THE PREPARATION OF PAROXETINE INTERMEDIATE
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A novel, improved, and enantiospecific process for the preparation of (-)-trans-4-(4-fluorophenyl)-3-hydroxymethyl-1-methylpiperidine of formula-(I), an advanced intermediate in the manufacture of antidepressant drug paroxetine is disclosed in the present invention. Compound of formula-(XXII) is prepared by resolution of compound of formula-(XX) using a chiral acid followed by hydrogenation of the resolved amine. Michael addition of the compound of formula-(XXII) onto acrylate esters gave the compounds of formula-(XXIII). Conversion of the hydroxy group present in compound of formula-(XXIII) into a leaving group followed by treatment with a strong base gave the enantiospecific intramolecularly cyclized piperidine derivative of formula-(XXV). Reduction of the ester group present in compound of formula-(XXV) with a metal hydride reducing agent gave the compound of formula-I with more than 97% chiral purity. Further purification of compound of formula-I to >99.5% is achieved by one recrystallization from a number of solvents. Present process is easily adaptable for commercial preparation of (-)-trans-4-(4-fluorophenyl)-3-hydroxymethyl-1-methylpiperidine of formula-(I).
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- PROCESS FOR PRODUCING PIPERIDINE COMPOUND
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The present invention.relates to a new process for preparing a pharmaceutical intermediate compound of formula (I). In the formula, Rl represents hydrogen, straight or branched C1-10 alkyl with or without substituent(s), straight or branched C1-10 alkoxy with or without substituent(s), aryl with or without substituent(s), formyl or alkylcarbonyl. Using the process according to the present invention, the intermediate compound for the preparation of aroxetine can be simply prepared with a high product yield and a high purity of 99% or more, without carrying out any dangerous processes.
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