反应详情

温度

80 °C

A mixture of tert-butyl 3(R)-amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepine-5-acetate (3.0 g), acetonitrile (100 ml), ethyl 6-(1-benzyloxycarbonyl-4-piperidyl)-2-chlorohexanoate (4.0 g), triethylamine (1.0 g) and potassium iodide (1.6 g) is stirred for 3 days at 80° C. Ethyl 6-(1-benzyloxycarbonyl-4-piperidyl)-2-chlorohexanoate (2.0 g) and potassium iodide (0.8 g) are added, and the stirring is continued for further 1 day at 80° C. The mixture is concentrated in vacuo, diluted with water (100 ml) and extracted with ethyl acetate (300 ml). The extract is washed with water, dried over anhydrous magnesium sulfate and evaporated in vacuo. Purification of the residual oil by silicagel column chromatography (hexane:ethyl acetate=2:1) gives tert-butyl 3(R)-[5-(1-benzyloxycarbonyl-4-piperidyl)-1(R)-ethoxycarbonylpentyl]amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepine-5-acetate (3.1 g) as a colorless oil and tert-butyl 3(R)-[5-(1-benzyloxycarbonyl-4-piperidyl)-1 (S)-ethoxycarbonylpentyl]amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepine-5-acetate (2.1 g) as a colorless oil.

1. waitthe stirring is continued for further 1 day at 80° C
2. concentrationThe mixture is concentrated in vacuo
3. additiondiluted with water (100 ml)
4. extractionextracted with ethyl acetate (300 ml)
5. washThe extract is washed with water
6. dry with materialdried over anhydrous magnesium sulfate
7. customevaporated in vacuo
8. customPurification of the residual oil by silicagel column chromatography (hexane:ethyl acetate=2:1)