- 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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- Tosylate salts of 4-(p-fluorophenyl)-piperidine -3-carbinols
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Tosylate salts are useful in purifying 4-(fluorophenyl)-3-carbinol-piperidines from the corresponding des-fluoro impurity. The purified compounds are advantageously used in paroxetine synthesis.
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- Process for producing piperidinecarbinols
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A process for producing a piperidinecarbinol represented by the general formula (2), which comprises reducing the trans isomer of a compound represented by the general formula (1): wherein R1is a hydrogen atom, a lower alkyl group or an aralkyl group, R2is a hydrogen atom, a lower alkyl group, an aryl group or an aralkyl group, and X is a hydrogen atom, a halogen atom, an alkyl group, an aryl group, an aralkyl group, an alkoxy group, a dialkylamino group, an alkylthio group, an arylthio group or CmF2m+1— wherein m is an integer of from 1 to 20.
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- Process for preparing aryl-piperidine carbinols and novel intermediates used in the process
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A process is disclosed for the preparation of a compound of formula (I): STR1 wherein Ar is aryl or substituted aryl and R3 is hydrogen, alkyl or aralkyl, which process comprises reducing a compound of formula (II): STR2 wherein Ar and R3 are as defined with respect to formula (I) and R4 is alkyl. Compounds of formula (I) are useful as chemical intermediates.
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