반응 #61109

반응 방정식

2-{(2S,3S)-2-[(R)-2-amino-2-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-acetylamino]-3-phenyl-butyrylamino}-thiazole-4-carboxylic acid methyl ester

diisopropylethylamine

diphosgene

toluene

→

2-{(2S,3S)-2-[(R)-4-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-2,5-dioxo-imidazolidin-1-yl]-3-phenyl-butyrylamino}-thiazole-4-carboxylic acid methyl ester

수율 55.0%

용매

ethyl acetate

tetrahydrofuran

tetrahydrofuran

반응 조건

후처리

1. 1
   세척The mixture was washed with water, brine
2. 2
   건조dried (sodium sulfate)
3. 3
   기타Evaporation of the solvents and chromatography of the residue over silica gel gradient
4. 4
   세척eluted with 0.2-1% methanol in dichloromethane

실험 절차

A solution of 2-{(2S,3S)-2-[(R)-2-amino-2-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-acetylamino]-3-phenyl-butyrylamino}-thiazole-4-carboxylic acid methyl ester (0.380 g, 0.75 mmol)) and diisopropylethylamine (0.52 mL, 3 mmol) in tetrahydrofuran (7.5 mL) were added to a solution of diphosgene (0.48 mL, 4 mmol) in a mixture of toluene (7.5 mol) and tetrahydrofuran (7.5 mol) over 10 minutes at 0° C. The mixture was stirred at 0° C. for 20 minutes and then diluted with ethyl acetate. The mixture was washed with water, brine and dried (sodium sulfate). Evaporation of the solvents and chromatography of the residue over silica gel gradient eluted with 0.2-1% methanol in dichloromethane gave (2-{(2S,3S)-2-[(R)-4-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-2,5-dioxo-imidazolidin-1-yl]-3-phenyl-butyrylamino}-thiazole-4-carboxylic acid methyl ester (0.22 g, 55%).

출처