反应详情

The t-butyl ester from step (b) above (11.97 g, 26.54 mmole) in dry dichloromethane (200 ml), under nitrogen, was treated with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (10.19 g, 53 mmole), 1-hydroxybenztriazole (3.94 g, 29 mmole), triethylamine (16.08 g, 22.15 ml, 159 mmole) and cis-4-aminocyclohexane-carboxylic acid ethyl ester hydrochloride (6.04 g, 20 mmole). After stirring overnight at room temperature, the solvent was evaporated and the residue partitioned between ethyl acetate and water. The organic phase was washed with dilute hydrochloric acid (2×), dilute aqueous sodium bicarbonate, water, dried (Na2SO4) and evaporated to yield the crude product (15.5 g). This was chromatographed on silica (400 g) eluting with 1 to 10% diethyl ether in dichloromethane. Evaporation of the desired fractions gave 3-{1-[(cis-4-ethoxycarbonyl-cyclohexyl)-carbamoyl]cyclopentyl}-2-(dibenzylaminomethyl)propanoic acid t-butyl ester as an oil (11.43 g, 71%). Found: C,73.38; H,8.87; N,4.42. C37H52N2O5 requires C,73.48; H,8.67; N,4.68%.

1. customthe solvent was evaporated
2. customthe residue partitioned between ethyl acetate and water
3. washThe organic phase was washed with dilute hydrochloric acid (2×), dilute aqueous sodium bicarbonate, water
4. dry with materialdried (Na2SO4)
5. customevaporated
6. customto yield the crude product (15.5 g)
7. customThis was chromatographed on silica (400 g)
8. washeluting with 1 to 10% diethyl ether in dichloromethane
9. customEvaporation of the desired fractions