Boron tribromide → HCID 118207396, compound

Participants

Reaction Steps

To a solution of 1-(4-fluorobenzyl)-3-(4-(4-methoxyphenyl)piperidin-1-yl)pyrrolidin-2-one (AJ) (3 g, 7.9 mmol) in dry dichloromethane (100 mL) under a N2 atmosphere at −78° C. was added 1 M boron tribromide in dichloromethane (39 mL, 39 mmol) and the resulting mixture was allowed to warm up to room temperature over 3 h, with stirring. The reaction was quenched with water (30 mL) and the organic layer was separated, washed with water and brine, and concentrated. The crude product was purified by flash chromatography on silica gel using 15% EtOAc in petroleum ether to yield racemic 1-(4-fluorobenzyl)-3-(4-(4-hydroxyphenyl)piperidin-1-yl)pyrrolidin-2-one (2.1 g, 73%); 1H NMR (400 MHz, DMSO-d6) δ ppm 1.49-1.74 (m, 4H) 1.90-2.11 (m, 2H) 2.24-2.42 (m, 2H) 2.65-2.80 (m, 2H) 2.99-3.23 (m, 3H) 3.40-3.54 (m, 1H) 4.27-4.46 (m, 2H) 6.61-6.70 (m, 2H) 6.95-7.04 (m, 2H) 7.17-7.31 (m, 4H) 9.10-9.16 (m, 1H). LCMS: R.T. 0.880 min. LCMS (ES-API), 369.2 m/z (M+H). A portion of the racemate (40 mg) was separated via SFC on a Chiralpak-IA 250 mm×4.6 mm, 5 microm column eluting with 35% solvent B, where solvent A=CO2 and solvent B=0.3% DEA in methanol at a total flow of 3 mL/min. Peak 1 showed a RT of 4.35 min and Peak 2 showed a RT of 6.29 min.

Provenance & Evidence