反应详情

N-methylmorpholine (5 equivalents, 6.0 mmol), EDC (2.5 equivalents, 3.0 mmol) and HOBt (2.5 equivalents, 3.0 mmol) are added slowly to a solution of N-(tert-butoxycarbonyl)-3-tert-butyl-D-alanine (1.0 equivalent, 1.2 mmol) and 3-(3-pyridyl)-L-alanine methyl ester (1.0 equivalent, 1.2 mmol) in dry dichloromethane (3 ml) at −30° C. The reaction mixture slowly (approx. 12 h) warms to room temperature, with complete conversion being observed by means of HPLC (method 36). The reaction mixture is worked up by diluting with dichloromethane (20 ml) and washing with saturated sodium bicarbonate solution (10 ml). The organic phase is dried with magnesium sulphate, filtered and concentrated. The crude product is purified by flash chromatography (silica gel, gradient dichloromethane 100% to dichloromethane/methanol: 4/1), resulting in 466 mg (96% of theory) of product.

1. customThe reaction mixture slowly (approx. 12 h)
2. customwarms to room temperature, with complete conversion
3. washwashing with saturated sodium bicarbonate solution (10 ml)
4. dry with materialThe organic phase is dried with magnesium sulphate
5. filtrationfiltered
6. concentrationconcentrated
7. customThe crude product is purified by flash chromatography (silica gel, gradient dichloromethane 100% to dichloromethane/methanol: 4/1)
8. customresulting in 466 mg (96% of theory) of product