(R)-3-Pyrrolidinol → (R)-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 1.3, 100 mg, 0.264 mmol), (R)-pyrrolidin-3-ol (46.1 mg, 0.529 mmol) and TEA (147 μL, 1.058 mmol) in DMSO (199 μL) was stirred at 90° C. for 16 h. The RM was diluted with TBME/EtOAc (1:1) (30 mL), washed with 0.5 M HCl (3×5 mL) and brine (5 mL) and the solvent was evaporated off under reduced pressure to give a crude product that was purified by flash chromatography (RediSep® Silica gel column, 4 g, cyclohexane/EtOAc-EtOH+0.1% NH4OH (8:2), from 30% to 80% EtOAc-EtOH+0.1% NH4OH (8:2)) to yield the title compound as an off-white solid. UPLC-MS (Condition 1) tR=2.83 min, m/z=444.9/446.9 [M+H]+, m/z=443.0/445.0 [M−H]−; 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.80-1.92 (m, 1H) 1.92-2.04 (m, 1H) 3.24-3.30 (m, 1H). 3.36-3.46 (m, 1H) 3.60-3.72 (m, 1H) 3.81 (dd, J=10.51, 4.65 Hz, 1H) 4.36 (d, J=2.69 Hz, 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) 7.80-7.90 (m, 3H) 8.14 (d, J=1.96 Hz, 1H) 10.19 (s, 1H).

Provenance & Evidence