1-(2-chloro-6-methylpyridin-4-yl)ethanone synthesis

Yield:890406-52-7 96%

Reaction Conditions:

in tetrahydrofuran at 0;

Steps:

2 : 1-(2-chloro-6-methylpyridin-4-yl)ethanone

To a solution of 2-chloro-N-methoxy-N,6-dimethylisonicotinamide (2.50 g, 11.7 mmol, Step-1) in THF (120 mL) is added dropwise a solution of methylmagnesium bromide in THF (0.99 M, 23.5 mL, 23.3 mmol) at 0 ^oC. After stirring at the same temperature, the mixture is poured into water (200 mL), and the aqueous layer is extracted with EtOAc (200 mL x 2). The combined organic layer is washed with brine, dried over sodium sulfate, and concentrated in vacuo to give 1.90 g (96% yield) of the title compound as a yellow oil. This is used for the next step without purification. ¹H-NMR (300 MHz, CDCl₃) delta 7.57 (1H, s), 7.51 (1H, s), 2.62 (3H, s), 2.60 (3H, s), MS (ESI) m/z: 170 (M+H)⁺.

References:

WO2013/161308,2013,A1 Location in patent:Paragraph 0188