반응 #61121

반응 방정식

diphosgene

2-{(2S,3S)-2-[(R)-2-(4-acetylamino-phenyl)-2-amino-acetylamino]-3-phenyl-butyrylamino}-thiazole-4-carboxylic acid methyl ester

→

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

수율 119.9%

용매

dichloromethane

ethyl acetate

dichloromethane

반응 조건

후처리

1. 1
   workup.ADDITIONdiisopropylethyllamine (72 μL, 0.41 mmol) was added
2. 2
   세척washed with 0.2M aqueous hydrochloric acid, saturated aqueous sodium bicarbonate, brine
3. 3
   건조dried over sodium sulfate
4. 4
   여과The solution was filtered
5. 5
   기타the solvent removed in vacu
6. 6
   기타The residue was purified by chromatography over silica gel gradient
7. 7
   세척eluted from 50% to 100% ethyl acetate in hexanes

실험 절차

Crude 2-{(2S,3S)-2-[(R)-2-(4-acetylamino-phenyl)-2-amino-acetylamino]-3-phenyl-butyrylamino}-thiazole-4-carboxylic acid methyl ester (≈0.175 mmol) was dissolved in dichloromethane (10 mL) and diisopropylethyllamine (72 μL, 0.41 mmol) was added. The resulting mixture was added to an ice cooled solution of diphosgene (13 μL, 0.109 mmol) in dichloromethane (10 mL). The reaction mixture was stirred for 15 minutes, diluted with ethyl acetate (100 mL) and washed with 0.2M aqueous hydrochloric acid, saturated aqueous sodium bicarbonate, brine and dried over sodium sulfate. The solution was filtered and the solvent removed in vacu. The residue was purified by chromatography over silica gel gradient eluted from 50% to 100% ethyl acetate in hexanes to afford 2-{(2S,3S)-2-[(R)-4-(4-acetylamino-phenyl)-2,5-dioxo-imidazolidin-1-yl]-3-phenyl-butyrylamino}-thiazole-4-carboxylic acid methyl ester (70 mg, 74%).

출처