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

Participants

Reaction Steps

To a suspension of 2-(3,3-bis(4-fluorophenyl)-2-oxopyrrolidin-1-yl)acetic acid (0.255 g, 0.771 mmol; Example 58D) in dichloromethane (3 mL) was added a catalytic amount of N,N-dimethylformamide followed by oxalyl dichloride (2.0 Min dichloromethane) (0.617 mL, 1.234 mmol). The reaction was stirred for 1 hour, after which a reddish solution resulted. The reaction was concentrated and dried under high vacuum. The residue was dissolved in dichloromethane (3 mL) and 6-(trifluoromethyl)pyridin-3-amine (0.100 g, 0.617 mmol) and 4-methylmorpholine (0.136 mL, 1.234 mmol) were added. After stirring for 1 hour, 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 60% ethyl acetate/hexanes (Flow=40 mL/minute) over 40 minutes to give the title compound. 1H NMR (300 MHz, CDCl3) δ 8.64 (s, 1H), 8.51 (d, J=2.5, 1H), 8.11 (dd, J=2.3, 8.7, 1H), 7.64-7.58 (m, 1H), 7.33-7.23 (m, 4H), 7.06-6.96 (m, 4H), 4.17 (s, 2H), 3.60 (t, J=6.5, 2H), 2.83 (t, J=6.5, 2H); MS (ESI+) m/z 476.0 (M+H)+.

Provenance & Evidence