反应详情

温度

-19.5 °C

To a solution of tert-butyl 6-methylpyridin-3-ylcarbamate (9 g, 43.2 mmol) in diethyl ether (150 mL) was added TMEDA (5.27 g, 6.85 mL, 45.4 mmol) and the solution was cooled down to −75° C. n-Butyl lithium (1.6 M solution in hexane, 72.1 mL, 115 mmol) was added dropwise over 20 minutes. The orange suspension was stirred for 1.25 hours at temperatures between −14 to −25° C. After cooling down to −75° C. a solution of iodine (16.8 g, 66.1 mmol) in diethyl ether (150 mL) was added dropwise over 45 minutes below −68° C. The resulting mixture was stirred at −75° C. for 30 minutes before stirring in an ice bath for 1.75 hours. The reaction mixture was poured on 10% aqueous Na2S2O3 solution (300 mL) and EtOAc (200 mL) and the layers were separated. The aqueous layer was extracted twice with EtOAc (100 mL). The organic layers were washed with 10% aqueous Na2S2O3 solution (100 mL) and brine (100 mL), dried over MgSO4, filtered, treated with silica gel (30 g) and evaporated. The compound was purified by silica gel chromatography on a 330 g column using a MPLC system eluting with a gradient of n-heptane:EtOAc (100:0 to 50:50). The impure fractions were combined, purified by silica gel chromatography on a 120 g column using an MPLC (Flasmaster) system eluting with a gradient of n-heptane:EtOAc (100:0 to 50:50). The product containing fractions were combined and evaporated until a suspension formed, which was filtered and washed with n-heptane. Colorless solid (2.84 g; 19%). MS (ESI): m/z=335.1 [M+H]+.

1. additionwas added dropwise over 20 minutes
2. additionwas added dropwise over 45 minutes below −68° C
3. stirringThe resulting mixture was stirred at −75° C. for 30 minutes
4. stirringbefore stirring in an ice bath for 1.75 hours
5. customthe layers were separated
6. extractionThe aqueous layer was extracted twice with EtOAc (100 mL)
7. washThe organic layers were washed with 10% aqueous Na2S2O3 solution (100 mL) and brine (100 mL)
8. dry with materialdried over MgSO4
9. filtrationfiltered
10. additiontreated with silica gel (30 g)
11. customevaporated
12. customThe compound was purified by silica gel chromatography on a 330 g column
13. washeluting with a gradient of n-heptane:EtOAc (100:0 to 50:50)
14. custompurified by silica gel chromatography on a 120 g column
15. washeluting with a gradient of n-heptane:EtOAc (100:0 to 50:50)
16. additionThe product containing fractions
17. customevaporated until a suspension
18. customformed
19. filtrationwhich was filtered
20. washwashed with n-heptane