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

Temperatur

25 °C

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).

1. customThe reaction was quenched slowly with 1N aq. citric acid solution at 0° C. until all solids
2. dissolutiondissolved
3. additionBrine was added
4. customthe two phases were separated
5. dry with materialThe organic phase was dried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated in vacuo

ORD-Eintrag

ord-ad05681ca1d1400888e4ea1c6faa1789

Quelldatensatz

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09000162B2