反应详情

温度

5.300000190734863 °C

To a 3 L 4-neck flask equipped with an overhead stirrer, nitrogen bubbler, and thermocouple was added 5-bromo-1-methyl-1H-imidazole (47.96 g, 297.9 mmol), followed by THF (537 mL). To this room temperature solution was added isopropylmagnesium chloride/lithium chloride complex (246.8 mL, 320.8 mmol, 1.3 M in THF) (addition temperature maintained between 16.6 and 25° C.) to afford a milky suspension and the reaction was stirred for 60 minutes and then cooled to 5.3° C. in an ice bath. To this mixture was added a solution of N-methoxy-N-methyl-6-(trifluoromethyl)nicotinamide (53.66 g, 229.1 mmol, Intermediate 4: step b) in THF (268 mL) (addition temperature between 5.3 and 5.6° C.) to afford an orange mixture. After addition, the reaction was warmed to room temperature over 2 hours. After stirring at room temperature for 18 hours, THF (200 mL) was added and the reaction was stirred for 2 hours. The reaction was then cooled to 4° C. with an ice bath and carefully quenched with 2 N aqueous HCl to pH=7, quenching temperature reached 12° C. The mixture was diluted with ethyl acetate (500 mL), the phases were separated, and the organic layer was washed with brine (2×200 mL) and dried over sodium sulfate, filtered and the solvent was removed. Hot ether was added and then filtered to give the title compound as a solid.

1. customTo a 3 L 4-neck flask equipped with an overhead stirrer
2. customto afford a milky suspension
3. customto afford an orange mixture
4. additionAfter addition
5. temperaturethe reaction was warmed to room temperature over 2 hours
6. stirringAfter stirring at room temperature for 18 hours
7. stirringthe reaction was stirred for 2 hours
8. temperatureThe reaction was then cooled to 4° C. with an ice bath
9. customcarefully quenched with 2 N aqueous HCl to pH=7
10. customquenching temperature
11. customreached 12° C
12. additionThe mixture was diluted with ethyl acetate (500 mL)
13. customthe phases were separated
14. washthe organic layer was washed with brine (2×200 mL)
15. dry with materialdried over sodium sulfate
16. filtrationfiltered
17. customthe solvent was removed
18. additionHot ether was added
19. filtrationfiltered