反应详情

温度

0 °C

N-Methoxy-N-methyl-6-(trifluoromethyl)nicotinamide (19.1 g, 81.6 mmol) was dissolved in tetrahydrofuran (410 mL). The system was purged with N2 and then cooled to 0° C. 1.4 M of methylmagnesium bromide in toluene/THF (75:25) (87.4 mL, 122.4 mmol) was added dropwise using an additional funnel. At the end of the addition the mixture was cloudy off-white. The mixture was stirred at 0° C. for 1 hour and carefully quenched by dropwise addition of 1 M aq. HCl (150 mL) and diluted with ethyl ether (300 mL) and EtOAc (100 mL). The organic layer was separated and washed with 0.1 M aq. NaOH (200 mL) and brine (2×50 mL), dried (Na2SO4), and concentrated to yield a light yellow solid (15.04 g, 98%).

1. customThe system was purged with N2
2. additionAt the end of the addition the mixture
3. customcarefully quenched by dropwise addition of 1 M aq. HCl (150 mL)
4. additiondiluted with ethyl ether (300 mL) and EtOAc (100 mL)
5. customThe organic layer was separated
6. washwashed with 0.1 M aq. NaOH (200 mL) and brine (2×50 mL)
7. dry with materialdried (Na2SO4)
8. concentrationconcentrated