Isolation of tramadol from Grignard reaction mixt. - by selective pptn. of hydrochloride salt

摘要

Isolation of trans-2-dimethylaminomethyl-1-(3-methoxyphenyl)-cyclohexanol hydrochloride of formula (I) from a reaction mixt. contg. the trans and cis isomers (of the free base) and Grignard reaction by-products, is effected by treating the mixt. with a soln. of HCl in a lower alcohol, or with HCl gas in the presence of an organic solvent (II), whereby (I) is selectively pptd. (II) is selected from alcohols of medium molecular wt., ketones, esters, ethers and aromatic ethers. USE/ADVANTAGE - Trans-2-dimethylaminomethyl-1-(3-methoxyphenyl)-cyclohexanol (tramadol) is a non-addictive analgesic (US3652589 and GB992399). The process is simpler than the prior art processes and avoids using hazardous dioxan. (I) with a purity of 86-99% may be obtained in yields of 38-66%.