Patent ID: 6437136
Filing Date: 2002-08-20
Classification: C07D

Abstract:
A process for preparing (âˆ’)cis-3-hydroxy-1-methyl-4-(2,4,6-trimethoxyphenyl)piperidine (II) comprising eitherresolving (3,4-cis)-3-(R,S)-hydroxy-1-methyl-4-(2,4,6-trimethoxyphenyl)piperidine (VIII) â€ƒto obtain the (âˆ’)cis-3-hydroxy-1-methyl-4-(2,4,6-trimethoxyphenyl)piperidine (II) in substantial enantiomeric purity; â€ƒor resolving at least one compound (Xa) or at least one compound (Xb) â€ƒwherein R is chosen from (C1-C16)-alkyl, (C6-C14)-aryl-(C1-C16)-alkyl, and (C6-C14)-aryl, and in the at least one compound (Xa), R is also optionally carboxy-(C2-C6)-alkyl, to form at least one resolved compound (Xa) or at least one resolved compound (Xb), and converting the at least one resolved compound (Xa) or the at least one resolved compound (Xb) into the (âˆ’)cis-3-hydroxy-1-methyl-4-(2,4,6-trimethoxyphenyl)piperidine (II) in substantial enantiomeric purity; â€ƒor resolving at least one ester (IXa) or at least one carbonate (IXb) â€ƒin which R is chosen from (C1-C16)-alkyl, (C6-C14)-aryl-(C1-C16)-alkyl, or (C6-C14)-aryl, and in the at least one ester (IXa) R is also optionally carboxy-(C2-C6)-alkyl, into a resolved product, and hydrogenating the resolved product to obtain the (âˆ’)cis-3-hydroxy-1-methyl-4-(2,4,6-trimethoxyphenyl)piperidine (II) in substantial enantiomeric purity; â€ƒor resolving isolated 3(R,S)-hydroxy-1-methyl-4-(2,4,6-trimethoxyphenyl)-1,2,3,6-tetrahydropyridine (VII) â€ƒto obtain a resolved isolated product, and hydrogenating the resolved isolated product to obtain the (âˆ’)cis-3-hydroxy-1-methyl-4-(2,4,6-trimethoxyphenyl)piperidine (II) in substantial enantiomeric purity.