Practical resolution of racemic trans-2-benzylaminocyclohexanol with di-p-toluoyl-l-tartaric acid via diastereomeric salt formation based on the Pope and Peachey method

A new resolution process for racemic trans-2-benzylaminocyclohexanol 2, a key intermediate for chiral pharmaceuticals, was investigated. Di-p-toluoyl-l-tartaric acid 15 was found to be a new practical resolving agent in terms of stability and productivity of the resolution system. Resolution conditions were optimized based on the Pope and Peachey method, and the best result was obtained when HCl was added to the resolution system as a supplemental acid; 2/l-15/HCl = 1.0/0.6/0.4 (mol/mol/mol) (yield 92%, 99.5%de, E 92%).

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(1R,2R)-2-Benzylaminocyclohexanol: di-p-toluoyl-l-tartaric acidC33H7NO9De >99.5%[α]D20=-110.3 (c 1, MeOH)Source of chirality: resolutionAbsolute configuration: (1R,2R/2R,3R)