Boron tribromide → 3-((3R,4R)-3-Fluoro-4-(3-fluoro-4-hydroxyphenyl)piperidin-1-yl)-1-(3-fluoro-4-methylbenzyl)pyrrolidin-2-one

Participants

Reaction Steps

To a stirred solution of 3-((3R,4R)-3-fluoro-4-(3-fluoro-4-methoxyphenyl)piperidin-1-yl)-1-(3-fluoro-4-methylbenzyl)pyrrolidin-2-one (diastereomeric pair from step L, 50 mg, 0.12 mmol) in DCM (5 mL) at −78° C. was added boron tribromide (2 mL, 2 mmol, 1 M in DCM) and the resulting mixture was stirred at rt for 3 h. The solvent was evaporated and the residue subjected to preparative HPLC (method D) to yield 20 mg (0.04 mmol, 37%) of 3-((3R,4R)-3-Fluoro-4-(3-fluoro-4-hydroxyphenyl)piperidin-1-yl)-1-(3-fluoro-4-methylbenzyl)pyrrolidin-2-one (diastereomeric pair). LCMS (Method K) RT 1.16 min; m/z 419 (M+H+); 1H NMR (400 MHz, methanol-d4) δ ppm 7.22-7.29 (m, 1H) 6.90-7.09 (m, 5H) 4.88-4.96 (m, 1H) 4.49-4.53 (m, 2H), 4.12-4.25 (m, 1H), 4.35-4.42 (m, 1H) 3.98-4.02 (m, 1H) 3.34-3.48 (m, 4H) 3.14-3.21 (m, 1H) 2.98-3.07 (m, 1H) 2.46-2.56 (m, 1H) 2.20-2.30 (m, 5H) 1.98-2.12 (m, 1H).

Provenance & Evidence