Hydrochloric Acid → 2-((S)-2-{(R)-4-[4-((R)-2,3-dihydroxy-propoxy)-phenyl]-2,5-dioxo-imidazolidin-1-yl}-3-phenyl-propionylamino)-thiazole-4-carboxylic acid methyl ester

Participants

Reaction Conditions

Reaction Steps

2-((S)-2-{(R)-2-Amino-2-[4-((S)-2,3-bis-trimethylsilanyloxy-propoxy)-phenyl]-acetylamino}-3-phenyl-propionylamino)-thiazole-4-carboxylic acid methyl ester (100 mg, 0.15 mmol) and diisoproylethylamine (0.078 ml, 0.45 mmol) in dichloromethane (2 mL) were added to a solution of diphosgene (0.0143 ml, 0.12 mmol) in dichloromethane (2 mL) over 10 minute at 0° C. The mixture was stirred at 0° C. for 20 minute, diluted with ethyl acetate, washed with saturated sodium bicarbonate, brine and dried over sodium sulfate. Evaporation of solvents gave an oil which was dissolved in tetrahydrofuran (2 mL), treated with 1 N aqueous hydrochloric acid (0.45 ml, 0.45 mmol) and stirred for 3 hours. The reaction was neutralized with saturated aqueous sodium bicarbonate and extracted with ethyl acetate. The organic extracts were washed with brine and dried over magnesium sulfate. The crude product was purified by chromatography over silica gel gradient eluted with 100% ethyl acetate up to 3% v/v methanol in ethyl acetate to give 2-((S)-2-{(R)-4-[4-((R)-2,3-dihydroxy-propoxy)-phenyl]-2,5-dioxo-imidazolidin-1-yl}-3-phenyl-propionylamino)-thiazole-4-carboxylic acid methyl ester as a solid (35 mg, 42%).

Provenance & Evidence