Process for preparing aminocyclohexyl ether compounds

摘要

The present invention relates to a process for preparing aminocyclohexyl ether compounds of Formula I: or the pharmaceutically acceptable salts and esters thereof. In particular, the instant invention is directed towards a process for preparing (1R,2R)-2-[(3R)-Hydroxypyrrolidinyl]-1-(3,4-dimethoxyphenethoxy)-cyclohexane as well as various intermediates.;

主权项

1. A process for preparing compounds of Formula I: where Y is selected from 3,4-dimethoxyphenyl, 3,4-dihydroxyphenyl or a 3,4-dihalophenyl, comprising the steps of:
a) Mixing a cyclohexyl amine (iv)  with a malic acid derivative (v)  where R2 is selected from hydrogen, esters, carbonates, carbamates, silyl ethers, phosphates or sulfates and where X and Z are independently selected from OH, C1-C6 alkoxy, esters, halides or O-acyl, said X and Z may ontionally be ioined to form a ring (v-a)to obtain a hydroxy succinimide (vi) b) isolating the hydroxy succinimide (vi) to provide an isolated hydroxy succinimide (vi); andc) reducing the isolated hydroxy succinimide (vi) to obtain a compound of Formula I.