반응 #1095897

반응 방정식

ammonium chloride

5-chloro-2,4-difluoro-6-(3,5-dimethylpiperidino) pyrimidine

sodium hydride

2-butyn-1-ol

→

5-chloro-4-(2-butynyloxy)-2-fluoro-6-(3,5-dimethyl piperidino)pyrimidine

수율 42.0%

용매

tetrahydrofuran

tetrahydrofuran

tetrahydrofuran

반응 조건

후처리

1. 1
   workup.STIRRINGstirred for 30 minutes at same temperature
2. 2
   추출the mixture was extracted with tert-butyl methyl ether three times
3. 3
   세척The organic layers were washed with a saturated sodium chloride aqueous solution
4. 4
   건조dried over anhydrous magnesium sulfate
5. 5
   농축concentrated

실험 절차

0.09 g of sodium hydride (60% oil suspension) was suspended in 2 ml of tetrahydrofuran. 0.3 ml of tetrahydrofuran solution of 0.13 g of 2-butyn-1-ol was added dropwise at room temperature therein, and the mixture was stirred for 10 minutes. Into the mixture was added dropwise 0.3 ml of tetrahydrofuran solution of 0.4 g of 5-chloro-2,4-difluoro-6-(3,5-dimethylpiperidino) pyrimidine at 0° C., and stirred for 30 minutes at same temperature. The reaction mixture was poured into a saturated ammonium chloride aqueous solution, and the mixture was extracted with tert-butyl methyl ether three times. The organic layers were washed with a saturated sodium chloride aqueous solution, dried over anhydrous magnesium sulfate and concentrated. The residue was subjected to silica gel column chromatography to obtain 0.20 g of 5-chloro-4-(2-butynyloxy)-2-fluoro-6-(3,5-dimethyl piperidino)pyrimidine (hereinafter, referred to as Compound (52)). Compound (52) had the cis/trans diastereomer originated two methyls on the pyperidine ring. The ratio of the cis/trans diastereomer was about 5/1.

출처