4-Methylmorpholine → N-(5-chloropyridin-2-yl)-2-(2-oxo-3-phenylpiperidin-1-yl)acetamide

Participants

Reaction Conditions

Reaction Steps

To a solution of 2-(2-oxo-3-phenylpiperidin-1-yl)acetic acid (0.100 g, 0.429 mmol; Example 91D) in dichloromethane (0.5 mL) was added oxalyl chloride (2.0 Min dichloromethane) (0.322 mL, 0.643 mmol) and a catalytic amount of N,N-dimethylformamide. After stirring for 30 minutes at 0° C., a reddish solution resulted. The reaction was concentrated, the residue was dissolved in dichloromethane (1 mL) and 5-chloropyridin-2-amine (0.047 g, 0.364 mmol) was added followed by N-methylmorpholine (0.071 mL, 0.643 mmol). After stirring for 1 hour, the reaction was loaded onto a silica gel column (SF15-24, Analogix®) and the product was eluted using a gradient of 25% ethyl acetate/hexanes to 70% ethyl acetate/hexanes over 30 minutes (Flow=30 mL/minute). Some color streaked through the column, so a second column was run under identical conditions to give the title compound. 1H NMR (300 MHz, CDCl3) δ 8.84 (s, 1H), 8.23 (d, J=2.7, 1H), 8.14 (d, J=8.8, 1H), 7.65 (dd, J=2.6, 8.9, 1H), 7.42-7.13 (m, 5H), 4.34-4.15 (m, 2H), 3.78 (dd, J=6.0, 7.9, 1H), 3.71-3.47 (m, 2H), 2.33-2.14 (m, 1H), 1.99 (m, 3H); MS (ESI+) m/z 344.0 (M+H)+.

Provenance & Evidence