反应详情

温度

0 °C

Diisopropylamine (0.868 mL, 6.14 mmol) was added dropwise to a stirring solution of 2.5M butyllithium in hexanes (2.339 mL, 5.85 mmol) in THF (20 mL) at −78° C. The solution was warmed to 0° C. for 10 minutes and then cooled again to −78° C. Cannulation of the LDA at −78° C. into (2R,6S)-4-(2-((tert-butyldiphenylsilyloxy)methyl)-4-chloro-5-fluoropyridin-3-yl)-2,6-dimethylmorpholine (Intermediate 45, 1.5 g, 2.92 mmol) in THF (10 mL) at −78° C. Allowed dark solution to stir for 20 minutes then cannulated into a stirring solution of 1-methyl-1H-imidazole-2-carbaldehyde (0.644 g, 5.85 mmol) in THF (10 mL) at −78° C. The solution was allowed to warm to −50° C. then quenched with saturated ammonium chloride solution. The mixture was extracted with ethyl acetate and washed resulting organics with brine. After drying the organics over sodium sulfate, filtering, and evacuating the filtrate under vacuum, a crude yellow oil was obtained. The crude oil was purified on silica using 40% ethyl acetate in n-hexane to give 1.2 g (66%) of the title compound as oil.

1. temperaturecooled again to −78° C
2. customat −78° C.
3. customat −78° C
4. temperatureto warm to −50° C.
5. customthen quenched with saturated ammonium chloride solution
6. extractionThe mixture was extracted with ethyl acetate
7. washwashed
8. customresulting organics with brine
9. dry with materialAfter drying the organics over sodium sulfate
10. filtrationfiltering
11. customevacuating the filtrate under vacuum
12. customa crude yellow oil was obtained
13. customThe crude oil was purified on silica using 40% ethyl acetate in n-hexane