Benzoic Acid → HCID 86597684, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of 400 mg (0.65 mmol) (2R,3S)-2-(3,5-bis-trifluoromethyl-phenyl)-N-[4-(4-fluoro-2-methyl-phenyl)-6-(3-hydroxy-2-hydroxymethyl-pyrrolidin-1-yl)-pyridin-3-yl]-N-methyl-isobutyramide in 6.5 ml tetrahydrofuran were added at 0° C. 0.67 ml (3.26 mmol) diisopropyl azodicarboxylate and 398 mg (3.26 mmol) benzoic acid. The reaction mixture was cooled to −78° C., followed by addition of 855 mg (3.26 mmol) triphenylphosphine. The reaction mixture was allowed to slowly warm to room temperature over night. Addition of 75 ml of a saturated sodium carbonate solution was followed by extraction with two 75-ml portions of tert-butyl methyl ether. The organic layers were washed with 75 ml brine, dried over sodium sulfate, concentrated in vacuo and purified by flash chromatography. The residue was dissolved in 20 ml methanol and treated with 0.1 ml of a 5.5 M sodium methylate solution in methanol. After stirring 3 h at room temperature the reaction mixture was concentrated in vacuo. The residue was dissolved in 75 ml dichloromethane and washed with 60 ml water, dried over sodium sulfate and purified by flash chromatography to give 117 mg (29%) of (2R,3R)-2-(3,5-bis-trifluoromethyl-phenyl)-N-[4-(4-fluoro-2-methyl-phenyl)-6-(3-hydroxy-2-hydroxymethyl-pyrrolidin-1-yl)-pyridin-3-yl]-N-methyl-isobutyramide as a white foam and 155 mg (40%) of (S)-2-(3,5-bis-trifluoromethyl-phenyl)-N-[4-(4-fluoro-2-methyl-phenyl)-6-(2-hydroxymethyl-2,5-dihydro-pyrrol-1-yl)-pyridin-3-yl]-N-methyl-isobutyramide as a white foam.

Provenance & Evidence