Reaktion #61121

Reaktionsgleichung

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

Ausbeute 119.9%

Lösungsmittel

dichloromethane

ethyl acetate

dichloromethane

Reaktionsbedingungen

Aufarbeitung

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

Vorschrift

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%).

Quelle