发明名称 |
ENANTIOSPECIFIC PROCESS FOR THE PREPARATION OF PAROXETINE INTERMEDIATE |
摘要 |
<p>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).</p> |
申请公布号 |
WO2005063707(A1) |
申请公布日期 |
2005.07.14 |
申请号 |
WO2004IN00247 |
申请日期 |
2004.08.18 |
申请人 |
NATCO PHARMA LIMITED;PULLA REDDY, MUDDASANI;RAJASEKHARA, REDDY PEDDI;VENKAIAH CHOWDARY, NANNAPANENI |
发明人 |
PULLA REDDY, MUDDASANI;RAJASEKHARA, REDDY PEDDI;VENKAIAH CHOWDARY, NANNAPANENI |
分类号 |
C07C215/30;C07C229/12;C07C309/66;C07D211/22;C07D211/60;C07D405/12;(IPC1-7):C07D211/60 |
主分类号 |
C07C215/30 |
代理机构 |
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代理人 |
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主权项 |
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地址 |
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