| 摘要 |
Preparation of biperiden comprises: (a) reacting exo-1-(bicyclo(2,2,1)-hept-5-en-2-yl)ethanone (III) with paraformaldehyde and piperidine to form a exo/endo mixture of 1-(bicyclo(2,2,1)-hept-5-en-2-yl)-3-piperidino-1-propanone (II); (b) reacting the mixture with phenylmagnesium compound (A), and (c) separating (I). 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: (a) reacting exo-1-(bicyclo(2,2,1)-hept-5-en-2-yl)ethanone (III), with paraformaldehyde and piperidine plus acid (or their adduct) to form an exo/endo mixture of 1-(bicyclo(2,2,1)-hept-5-en-2-yl)-3-piperidino-1-propanone (II); (b) reacting the mixture with phenylmagnesium compound (A) and (c) separating (I) from the resulting isomer mixture. (III) Is prepared by: (i) reacting cyclopentadiene and methyl vinyl ketone; (ii) optionally removing low boilers by distillation to give a mixture of exo- and endo-(III); (iii) treating the mixture with an alkali 1-4C alkanoate and (iv) fractional distillation to recover exo-(III). An Independent claim is also included for (II) with an exo/endo ratio of 2.5-4:1.
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