| 摘要 |
Preparation of biperiden (I; a mixture of 1-(bicyclo(2,2,1)hept-5-en-2-yl(exoR))-1-phenyl-3-piperidinopropanol (1,S) and the corresponding (exoS)/(1,R) compound) comprises reacting 1-(bicyclo(2,2,1)-hept-5-en-2-yl)-3-piperidino-1-propanone (II), of exo/endo ratio at least 4.5:1, with a phenylmagnesium compound (A). Preparation of biperiden (I; mixture of 1-(bicyclo(2,2,1)hept-5-en-2-yl(exoR))-1-phenyl-3-piperidinopropanol (1,S) and the corresponding (exoS)/(1,R) compound) comprises reacting 1-(bicyclo(2,2,1)-hept-5-en-2-yl)-3-piperidino-1-propanone (II), of exo/endo ratio of at least 4.5:1, with a phenylmagnesium compound (A). (II) Is prepared by reacting exo-1-(bicyclo(2,2,1)-hept-5-en-2-yl)ethanone (III) with a source of formaldehyde and an acid salt of piperidine (or with piperidine in the presence of acid) in organic solvent, optionally mixed with water. The reaction mixture is poured into water and extracted with a water-immiscible or sparingly miscible solvent at upto pH 7, then the aqueous raffinate is extracted similarly at pH at least 7.5. This extract is separated, purified by acid extraction and the solvent removed to give the exo/endo-(II) mixture. An Independent claim is also included for (II) having an exo/endo ratio at least 4.5:1.
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