(3S)-pyrrolidin-3-ol → (S)-3-Bromo-4-(3-hydroxypyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)benzamide

Participants

Reaction Conditions

Reaction Steps

A mixture of 3-bromo-4-fluoro-N-(4-(trifluoromethoxy)phenyl)benzamide (Stage 1.2, 100 mg, 0.264 mmol), (S)-pyrrolidin-3-ol (46.1 mg, 0.529 mmol) and TEA (147 μL, 1.058 mmol) in DMSO (200 μL) was stirred at 90° C. for 16 h. The RM was diluted with 30 mL of TBME/EtOAc (1:1), sequentially washed 5 times with 0.5 M HCl and brine then evaporated to dryness under reduced pressure. The crude product was purified by flash column chromatography (RediSep® Silica gel column, 12 g, cyclohexane/EtOAc-EtOH+0.1% NH4OH (9:1), from 10% to 50% EtOAc-EtOH+0.1% NH4OH (9:1)) to afford the title compound as a white solid. UPLC-MS (condition 1) tR 2.83 min, m/z=444.9 [M+H]+, m/z=443.0 [M−H]−; 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.79-1.92 (m, 1H) 1.91-2.04 (m, 1H) 3.27 (d, J=10.76 Hz, 1H) 3.34-3.45 (m, 1H) 3.67 (dd, 1H) 3.81 (dd, J=10.39, 4.77 Hz, 1H) 4.30-4.42 (m, 1H) 4.97 (d, J=3.42 Hz, 1H) 6.93 (d, J=8.80 Hz, 1H) 7.34 (d, J=8.56 Hz, 2H) 7.81-7.90 (m, 3H) 8.13 (d, J=2.20 Hz, 1H) 10.18 (s, 1H).

Provenance & Evidence