反応 #8274

反応方程式

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

収率 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

収率 68.0%

溶媒

N,N-dimethylformamide

N,N-dimethylformamide

N,N-dimethylformamide

反応条件

後処理

1. 1
   温度cooled to 0° under nitrogen
2. 2
   温度the mixture heated to 40° for 5 hours
3. 3
   温度After cooling
4. 4
   抽出extracted with dichloromethane (4×20 ml)
5. 5
   乾燥The organic phase was dried (magnesium sulfate)
6. 6
   その他evaporated
7. 7
   その他crude product purified by chromatography on a 10 g silica Mega Bond Elut® column
8. 8
   洗浄eluting with a gradient from 50% to 75% ethyl acetate in isohexane

実験手順

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).

出典