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-H2O 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 CH2Cl2 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: EIMS m/z 139 ([M]+). 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-49482264c9de4a81afc79aaf8c0269c5

Quelldatensatz

uspto-grants-2013_06

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08461164B2