反应详情

温度

0 °C

A n-BuLi solution (1.89 mL, 3.03 mmol, 1.6 M solution in hexane) was slowly added to a −78° C. solution of 5-bromo-2-methoxypyridine (0.392 mL, 3.03 mmol) in dry THF (10 mL). After addition, stirring was continued for an additional 40 minutes and N-methoxy-N-methylthiazole-5-carboxamide (0.600 g, 3.48 mmol, Intermediate 11: step a) dissolved in THF (10 mL) was slowly added. The mixture was stirred at −78° C. for 10 minutes then warmed to 0° C. and stirred for 1 hour. The cold solution was quenched with saturated aqueous NH4Cl and warmed to room temperature. H2O was added and layers were separated. The aqueous layer was extracted with EtOAc (3×) and the combined organic extracts washed with brine, dried (Na2SO4), filtered, evaporated in vacuo, preabsorbed onto silica gel and chromatographed (CH2Cl2/EtOAc) to provide product. The pure white solid title compound was precipitated from MeOH, filtered and dried under reduced pressure.

1. additionAfter addition
2. additionwas slowly added
3. stirringThe mixture was stirred at −78° C. for 10 minutes
4. stirringstirred for 1 hour
5. customThe cold solution was quenched with saturated aqueous NH4Cl
6. temperaturewarmed to room temperature
7. additionH2O was added
8. customlayers were separated
9. extractionThe aqueous layer was extracted with EtOAc (3×)
10. washthe combined organic extracts washed with brine
11. dry with materialdried (Na2SO4)
12. filtrationfiltered
13. customevaporated in vacuo
14. custompreabsorbed onto silica gel
15. customchromatographed (CH2Cl2/EtOAc)
16. customto provide product
17. customThe pure white solid title compound was precipitated from MeOH
18. filtrationfiltered
19. customdried under reduced pressure