반응 #8274

반응 방정식

water

Sodium hydride

3-(4(1-(2,2-dimethyl-1,3-dioxolan-4(S)-ylcarbonyl)-1,2,5,6-tetrahydropyrid-4-yl)-3,5-difluorophenyl)-5(R)-methanesulfonyloxymethyloxazolidin-2-one

5-(t-butoxycarbonylamino)-3-methylisoxazole

→

desired product

수율 68.0%

3-(4-(1-(2,2-Dimethyl-1,3-dioxolan-4(S)-ylcarbonyl)-1,2,5,6-tetrahydropyrid-4-yl)-3,5-difluorophenyl)-5(R)-(N-(t-butoxycarbonyl)-3-methylisoxazol-5-ylaminomethyl)oxazolidin-2-one

수율 68.0%

용매

N,N-dimethylformamide

N,N-dimethylformamide

N,N-dimethylformamide

반응 조건

후처리

1. 1
   온도cooled to 0° under nitrogen
2. 2
   온도the mixture heated to 40° for 5 hours
3. 3
   온도After cooling
4. 4
   추출extracted with dichloromethane (4×20 ml)
5. 5
   건조The organic phase was dried (magnesium sulfate)
6. 6
   기타evaporated
7. 7
   기타crude product purified by chromatography on a 10 g silica Mega Bond Elut® column
8. 8
   세척eluting with a gradient from 50% to 75% ethyl acetate in isohexane

실험 절차

Sodium hydride (60% in oil, 72 mg, 1.8 mM) was suspended in dry N,N-dimethylformamide (3 ml), cooled to 0° under nitrogen, and a solution of 5-(t-butoxycarbonylamino)-3-methylisoxazole (356 mg, 1.8 mM) in N,N-dimethylformamide (3 ml) added. After stirring for 10 minutes, a solution of 3-(4(1-(2,2-dimethyl-1,3-dioxolan-4(S)-ylcarbonyl)-1,2,5,6-tetrahydropyrid-4-yl)-3,5-difluorophenyl)-5(R)-methanesulfonyloxymethyloxazolidin-2-one (516 mg, 1.5 mM) in N,N-dimethylformamide (3 ml) was added, and the mixture heated to 40° for 5 hours. After cooling, the mixture was poured into water (50 ml), extracted with dichloromethane (4×20 ml). The organic phase was dried (magnesium sulfate), evaporated and crude product purified by chromatography on a 10 g silica Mega Bond Elut® column, eluting with a gradient from 50% to 75% ethyl acetate in isohexane. Relevant fractions were combined to give the desired product (420 mg).

출처