Conversion of a racemic mixture of 8-chloro-2-(2,6-difluorophenylmethyl)-2,3-dihydro-3-methyl-1,2,5-benzothiadiazepin-4(5h)-one 1,1-dioxide into a single enantiomer via a chromatographic resolution/racemization method

A simple and efficient strategy to convert the racemic mixture of 8-chloro-2-(2,6-difluorophenylmethyl)-2,3-dihydro-3-methyl-1,2,5-benzothiadiazepin-4(5H)-one 1,1-dioxide, a new anti-HIV-1 agent targeted to reverse transcriptase, into the more active (S)-enantiomer is described. The method utilizes repetition of the following two steps: 1) semipreparative enantioseparation by HPLC on chiral stationary phase; 2) base-induced racemization of the less active (R)-enantiomer.