反应详情

温度

0 °C

Diisopropylamine (0.925 mL, 6.55 mmol) was added dropwise to a stirring solution of 2.5M n-butyllithium in hexane (2.495 mL, 6.24 mmol) in THF (10 mL) at −78° C. Allowed solution to warm to 0° C. for 10 minutes then cooled again to −78° C. Cannulated the prepared LDA at −78° C. into (2R,6S)-4-(2-((tert-butyldiphenylsilyloxy)methyl)-4-chloro-5-fluoropyridin-3-yl)-2,6-dimethylmorpholine (Intermediate 45, 1.6 g, 3.12 mmol) in THF (10 mL) at −78° C. Allowed the dark solution to stir for 20 minutes and then cannulated into a stirring solution of N-methoxy-N-methylpicolinamide (1.05 g, 6.24 mmol) in THF (10 mL) at −78° C. Allowed the solution to warm to −50° C. and then quenched with saturated ammonium chloride solution. Extracted mixture with ethyl acetate and washed resulting organics with brine. Dried organics over sodium sulfate, filtered, and evacuated filtrate under vacuum to give crude yellow oil. The crude oil was purified on silica using 10-30% acetone in n-hexane as eluant to give 1.3 g (67%) of the title compound as oil.

1. temperaturethen cooled again to −78° C
2. customat −78° C.
3. customat −78° C
4. temperatureAllowed the solution to warm to −50° C.
5. customquenched with saturated ammonium chloride solution
6. extractionExtracted mixture with ethyl acetate
7. washwashed
8. customresulting organics with brine
9. filtrationDried organics over sodium sulfate, filtered
10. customevacuated filtrate under vacuum
11. customto give crude yellow oil
12. customThe crude oil was purified on silica using 10-30% acetone in n-hexane as eluant