反应详情

温度

20 °C

A solution of 4-chloro-6-[(1E)-3,3-diethyltriaz-1-en-1-yl]-5-ethynyl-3′-fluoro-N-methoxy-N-methylbiphenyl-2-carboxamide (2.7 g, 6.6 mmol) in tetrahydrofuran (26 mL) at 0° C. was treated with 3 M of methylmagnesium chloride in tetrahydrofuran (6.6 mL, 20 mmol) dropwise and stirred at 20° C. for 1 hour. The reaction mixture still contained some starting material and was, therefore, cooled to 0° C., treated with additional 3 M of methylmagnesium chloride in tetrahydrofuran (2.2 mL, 6.6 mmol) dropwise, and stirred at 20 ° C. for 2 hours. The reaction mixture was cooled to 0° C., quenched with 1 M hydrogen chloride in water (26 mL, 26 mmol), poured into 0.1 M hydrogen chloride in water (100 mL) and extracted with ethyl acetate (150 mL). The organic layer was separated, washed with saturated sodium bicarbonate and brine, dried with sodium sulfate, filtered, and concentrated to give a crude oil. Purification by flash column chromatography using ethyl acetate in hexanes (0%-20%) gave the desired product (2.3 g, 93%). LCMS for C20H20ClFN3O (M+H)+: m/z=372.1; Found: 371.9.

1. temperaturecooled to 0° C.
2. stirringstirred at 20 ° C. for 2 hours
3. temperatureThe reaction mixture was cooled to 0° C.
4. extractionextracted with ethyl acetate (150 mL)
5. customThe organic layer was separated
6. washwashed with saturated sodium bicarbonate and brine
7. dry with materialdried with sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated
10. customto give a crude oil
11. customPurification by flash column chromatography