4-Methylmorpholine → 2-[3,3-bis(4-fluorophenyl)-2-oxopyrrolidin-1-yl]-N-[6-(trifluoromethyl)pyridin-2-yl]acetamide

Participants

Reaction Steps

To a suspension of 2-(3,3-bis(4-fluorophenyl)-2-oxopyrrolidin-1-yl)acetic acid (0.192 g, 0.578 mmol; Example 58D) in dichloromethane (3 mL) was added a catalytic amount of N,N-dimethylformamide followed by oxalyl dichloride (2.0 Min dichloromethane) (0.578 mL, 1.157 mmol). The reaction was stirred for 30 minutes than concentrated to give an oil. After drying under high vacuum for 20 minutes, the residue was dissolved in dichloromethane (1 mL) and 6-(trifluoromethyl)pyridin-2-amine (0.075 g, 0.463 mmol) and 4-methylmorpholine (0.102 mL, 0.925 mmol) were added. After stirring for 20 minutes, the reaction was loaded onto a GraceResolv™ 40 g silica gel column (Grace Davison Discovery Sciences) and the product eluted with a gradient of 5% ethyl acetate/hexanes to 35% ethyl acetate/hexanes (Flow=40 mL/minute) over 30 minutes to give the title compound. 1H NMR (300 MHz, CDCl3) δ 8.36 (s, 1H), 8.32 (d, J=8.5, 1H), 7.86 (t, J=8.0, 1H), 7.43 (d, J=7.3, 1H), 7.36-7.29 (m, 4H), 7.06-6.96 (m, 4H), 4.22 (s, 2H), 3.54 (t, J=6.5, 2H), 2.83 (t, J=6.5, 2H); MS (ESI+) m/z 476.1 (M+H)+.

Provenance & Evidence