Acetic Anhydride → N-[1-(5-Fluoropyridin-2-yl)ethenyl]acetamide

Participants

Reaction Conditions

Reaction Steps

A solution of MeMgBr (170.3 ml, 510.98 mmol) in ether was diluted with 170 ml of anhydrous THF and cooled to 0° C. 5-fluoropyridine-2-carbonitrile (Intermediate 1, 53.6 g, 425.82 mmol) in THF (170 ml) was added dropwise. The reaction was stirred at 0° C. for 30 minutes, then diluted with dichloromethane (170 ml). Acetic anhydride (48.3 ml, 510.98 mmol) in dichloromethane (100 ml) was added dropwise at 0° C. After addition, the reaction was warmed to room temperature and stirred at room temperature for 8 hours. Saturated sodium bicarbonate solution (50 ml) was added and extracted with EtOAc (2×200 ml). The combined organic was dried over sodium sulfate. After removal of solvent, the resulted residue was purified by column chromatography (hexane:EtOAc=2.5:1) to give the title compound as a white solid (26.6 g, 35%). 1H NMR (400 MHz) δ 9.37 (s, 1H), 8.57 (d, J=2.8 Hz, 1H), 7.81 (m, 2H), 6.01 (s, 1H), 5.52 (s, 1H), 2.08 (s, 3H). MS: Calculated: 180. Found: [M+H]+ 181.

Provenance & Evidence