Reacción #61109

Ecuación de reacción

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

Rendimiento 55.0%

Disolventes

ethyl acetate

tetrahydrofuran

tetrahydrofuran

Condiciones de reacción

Tratamiento posterior

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

Procedimiento

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%).

Fuente