反应详情

0.94 M solution of diisobutylaluminium hydride in hexane (38.3 ml) was added dropwise to a solution of methyl 5-{[(3R)-1-benzyl-3-pyrrolidinyl](tert-butoxycarbonyl)amino}-2-pyrazinecarboxylate (8.42 g) in THF (170 ml) with stirred below −60° C. under atmospheric pressure of nitrogen, and the reaction mixture was stirred at −55 to −50° C. for 1 hr. To the reaction mixture was added saturated aqueous ammonium chloride (10.2 ml) at the same temperature, then the mixture was stirred at 25° C. for 40 minutes. THF (60 ml) and MgSO4 (34.1 G) were added to the solution, and the mixture was stirred at 25° C. for 15 minutes. The reaction mixture was filtrated, the filtrate was Filtrate (A). On the other hand, to an ice-cooled suspension of sodium hydride (938 mg) in THF (90 ml) was added ethyl (diethoxyphosphoryl)acetate (5.26 g), and the mixture was stirred at 25° C. for 1 hr. To the mixture was added Filtrate (A) at 25° C., the reaction mixture was stirred at same temperature for 30 minutes. The reaction mixture was poured into a mixture of AcOEt and 5% aqueous NaCl. The separated organic layer was washed with brine, dried over sodium sulfate and evaporated in vacuo. The resulting residue was purified by column chromatography on silica gel (116 g) using a mixed solvent of hexane and ethyl acetate (5:1 to 1:1). The fractions containing the objective compound were collected and evaporated under reduced pressure. Title compound (6.74 g, 73%), was obtained as slightly yellowish oil.

1. stirringthe reaction mixture was stirred at −55 to −50° C. for 1 hr
2. stirringthe mixture was stirred at 25° C. for 40 minutes
3. stirringthe mixture was stirred at 25° C. for 15 minutes
4. filtrationThe reaction mixture was filtrated
5. temperatureOn the other hand, to an ice-cooled
6. additionsuspension of sodium hydride (938 mg) in THF (90 ml)
7. additionwas added ethyl (diethoxyphosphoryl)acetate (5.26 g)
8. stirringthe mixture was stirred at 25° C. for 1 hr
9. additionTo the mixture was added Filtrate (A) at 25° C.
10. stirringthe reaction mixture was stirred at same temperature for 30 minutes
11. additionThe reaction mixture was poured into a mixture of AcOEt and 5% aqueous NaCl
12. washThe separated organic layer was washed with brine
13. dry with materialdried over sodium sulfate
14. customevaporated in vacuo
15. customThe resulting residue was purified by column chromatography on silica gel (116 g)
16. additionThe fractions containing the objective compound
17. customwere collected
18. customevaporated under reduced pressure