반응 #85125

반응 방정식

sodium hydride

sodium hydride

4-[5-chloro-2-(difluoromethoxy)phenyl]-5-methoxypyridin-2(1H)-one

ethyl 2-{[(trifluoromethyl)sulphonyl]oxy}butanoate

ethyl 2-{[(trifluoromethyl)sulphonyl]oxy}butanoate

→

Ethyl 2-{4-[5-chloro-2-(difluoromethoxy)phenyl]-5-methoxy-2-oxopyridine-1(2H)-yl}butanoate

용매

tetrahydrofuran

반응 조건

후처리

1. 1
   workup.ADDITIONwere then added dropwise
2. 2
   workup.STIRRINGthe reaction mixture was stirred at RT for 5 min
3. 3
   workup.STIRRINGthe reaction mixture was stirred at RT for 15 min
4. 4
   기타quenched with water
5. 5
   기타After phase separation
6. 6
   추출the aqueous phase was extracted twice with ethyl acetate
7. 7
   세척The combined organic phases were washed with saturated aqueous sodium chloride solution
8. 8
   건조dried (sodium sulphate)
9. 9
   여과filtered
10. 10
    농축concentrated under reduced pressure
11. 11
    기타The residue was purified by flash chromatography (silica gel 50, cyclohexane/ethyl acetate gradient)

실험 절차

Under argon and at RT, 105 mg (2.64 mmol, 1.3 eq.) of sodium hydride (60% in mineral oil) were added to a solution of 618 mg (2.03 mmol) of 4-[5-chloro-2-(difluoromethoxy)phenyl]-5-methoxypyridin-2(1H)-one in 25 ml of tetrahydrofuran, the mixture was stirred at RT for 60 min 871 mg (2.64 mmol, 1.3 eq.) of ethyl 2-{[(trifluoromethyl)sulphonyl]oxy}butanoate (racemate) [J. Castells et al. Tetrahedron, 1994, 50, 13765-13774] were then added dropwise and the mixture was stirred at RT for 1 h. A further 38 mg (0.96 mmol) of sodium hydride (60% in mineral oil) were added, the reaction mixture was stirred at RT for 5 min, a further 871 mg (2.64 mmol, 1.3 eq.) of ethyl 2-{[(trifluoromethyl)sulphonyl]oxy}butanoate (racemate) were added dropwise, and the reaction mixture was stirred at RT for 15 min and then quenched with water. After phase separation, the aqueous phase was extracted twice with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried (sodium sulphate), filtered and concentrated under reduced pressure. The residue was purified by flash chromatography (silica gel 50, cyclohexane/ethyl acetate gradient). Yield: 415 mg (48% of theory)

출처