Diethyl Ether → 1-(2-Fluoro-4-pyridinyl)ethanone

Participants

Reaction Conditions

Reaction Steps

To a solution of 2-fluoroisonicotinonitrile (10 g, 82 mmol) in anhydrous Et2O (250 mL) cooled in an ice-water bath was slowly added 3M methyl magnesium bromide in hexane (40 mL, 120 mmol). The mixture was stirred at 25° C. overnight. The reaction was quenched slowly with 1N aq. citric acid solution at 0° C. until all solids dissolved. Brine was added and the two phases were separated. The organic phase was dried over Na2SO4, filtered, and concentrated in vacuo to give 1-(2-fluoropyridin-4-yl)-ethanone (6.2 g) as a brown oil. The aqueous phase was stirred at 25° C. for 3 h, then extracted with CH2Cl2. The dichloromethane layer was dried over Na2SO4, filtered, and concentrated in vacuo to give an additional 1.1 g of the product, for a total of 7.3 g, used in the next step without further purification. MS m/z 139. 1H NMR (CDCl3): δ 8.25 (dd, 1H), 7.47 (d, 1H), 7.21 (m, 1H).

Provenance & Evidence