반응 #61107

반응 방정식

1-Hydroxybenzotriazole

2-((2S,3S)-2-Amino-3-phenyl-butyrylamino)-thiazole-4-carboxylic acid methyl ester

(2R)-tert-butoxycarbonylamino-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-acetic acid

O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium

diisopropylethyl amine

→

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

용매

ethyl acetate

N,N-dimethylformamide

N,N-dimethylformamide

반응 조건

후처리

1. 1
   세척the mixture was washed with water and brine
2. 2
   workup.ADDITIONThe organic layer was diluted with an equal volume of dichloromethane
3. 3
   여과filtered through a pad of silica gel with a layer of sodium sulfate on the top
4. 4
   세척eluted with 1:1 ethyl acetate/dichloromethane
5. 5
   기타Evaporation of the solvents
6. 6
   기타gave a white solid which
7. 7
   기타was triturated with ether/hexane

실험 절차

2-((2S,3S)-2-Amino-3-phenyl-butyrylamino)-thiazole-4-carboxylic acid methyl ester (0.255 g, 0.80 mmol), (2R)-tert-butoxycarbonylamino-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-acetic acid (prepared according to the procedure of Bohme, E. H. W. et al., J. Med. Chem. 1980, 23,405-412), O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium hexaflurorophosphate (0.364 g, 0.96 mmol) and diisopropylethyl amine (0.56 mol, 3.2 mmol) were dissolved in N,N-dimethylformamide (3 mL) in an ice bath. 1-Hydroxybenzotriazole (0.13 g, 9.6 mmol) in N,N-dimethylformamide (1 mL) was added dropwise. Stirring was continued for 30 min at 0° C. The reaction mixture was diluted with ethyl acetate and the mixture was washed with water and brine. The organic layer was diluted with an equal volume of dichloromethane, filtered through a pad of silica gel with a layer of sodium sulfate on the top and eluted with 1:1 ethyl acetate/dichloromethane. Evaporation of the solvents gave a white solid which was triturated with ether/hexane to give crude 2-{(2S,3S)-2-[(R)-2-tert-butoxycarbonylamino-2-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-acetylamino]-3-phenyl-butyrylamino}-thiazole-4-carboxylic acid methyl ester (0.49 g).

출처