Resolution of 1-[2-carboxy-6-(trifluoromethyl)phenyl]-1H-pyrrole-2-carboxylic acid with methyl (R)-2-phenylglycinate, reciprocal resolution and second order asymmetric transformation

A novel, highly efficient method has been developed for the separation of the optical isomers of 1-[2-carboxy-6-(trifluoromethyl)phenyl]-1H-pyrrole-2-carboxylic acid with methyl (R)-2-phenylglycinate. The structural aspects of chiral discrimination have been discussed via comparison of the molecular structures and the packing energies of the diastereoisomeric salts determined by single crystal X-ray diffraction measurements. Reciprocal resolution and a new, highly efficient second order asymmetric transformation of racemic methyl 2-phenylglycinate with the pure enantiomer of the previously resolved atropisomeric carboxylic acid are also reported.

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(Sa)-1-[2-Carboxy-6-(trifluoromethyl)phenyl]-1H-pyrrole-2-carboxylic acidC13H8F3NO4ee 96% (HPLC)[α]D25=-43.1 (c 1.0, EtOH)Source of chirality: resolution with methyl (R)-2-phenyl-glycinateAbsolute configuration: (Sa)

Methyl (R)-2-phenylglycinateC9H11NO2ee 95% (HPLC)[α]D25=-154 (c 1.0, EtOH)Source of chirality: resolution with (S)-1-[2-carboxy-6-(trifluoromethyl)phenyl]-1H-pyrrole-2-carboxylic acidAbsolute configuration: (R)