Dimethylcarbamoyl Chloride → HCID 90203294, compound

Participants

Reaction Steps

To a solution of 3-cyclopropyl-4-(2-fluoro-1-methyl-ethoxy)pyridine (example 287b, 6.26 g, 32.1 mmole) in dichloromethane (100 mL) was added m-cpba 77% (10.8 g, 48.1 mmole) and the reaction was stirred at room temperature for 16 hours. Reaction mixture was diluted with dichloromethane and extracted with a 1M aqueous solution of sodium bicarbonate. Organic phase was collected and the aqueous phase was back-extracted with dichloromethane. Combined organic phases were dried over magnesium sulfate and evaporated down to dryness. The crude pyridine-oxide intermediate (6.97 g) was used without any purification. To a solution of the crude pyridine-oxide (6.97 g, 33.0 mmole) in dichloromethane (110 mL) was added dimethylcarbamoylchloride (CAN 79-44-7, 5.32 g, 4.55 mL, 49.5 mmole) and trimethylsilylcyanide (8.18 g, 10.3 mL, 82.5 mmole). The reaction mixture was stirred at room temperature for 16 hours and the reaction was quenched by addition of a 1M aqueous solution of sodium bicarbonate. The bi-phasic mixture was vigorously stirred for 10 minutes and then poured into a separatory funnel. The organic phase was extracted and collected. The aqueous phase was back-extracted with dichloromethane. Combined organic phases were dried over magnesium sulfate and evaporated down to dryness. The crude material was purified by flash chromatography on silica eluting with a gradient of heptane and ethyl acetate to yield the title compound (1.5 g, 21%). MS (ESI, m/z): 221.6 (M+H+).

Provenance & Evidence