反应详情

HOBt (4 equivalents, 2038 mg, 15.08 mmol), N-methylmorpholine (3 equivalents, 11.3 mmol), N-benzyloxycarbonyl-D-leucine (1.0 equivalent, 1000 mg, 3.8 mmol), EDC (2 equivalents, 1441 mg, 7.5 mmol) and again N-methylmorpholine (2 equivalents, 7.5 mmol) are added successively at −10° C. to a solution of L-leucine methyl ester hydrochloride (1.1 equivalents, 753.2 mg, 4.15 mmol) in dichloromethane p.a. (20 ml). The reaction mixture warms slowly (about 12 h) to RT, whereby complete conversion of the amine component is observed by means of HPLC. The reaction mixture is concentrated, taken up in ethyl acetate (about 200 ml) and then washed with a saturated aqueous sodium hydrogen carbonate solution (once), 5% aqueous citric acid (twice), a saturated aqueous sodium hydrogen carbonate solution (once) and a saturated sodium chloride solution. The mixture is dried over sodium sulfate and filtered. The mixture is evaporated to dryness in vacuo and then dried further under high vacuum. 1483 mg (93% of theory) of the title compound are obtained, which is reacted without further purification.

1. customThe reaction mixture warms slowly (about 12 h)
2. customto RT
3. concentrationThe reaction mixture is concentrated
4. washwashed with a saturated aqueous sodium hydrogen carbonate solution (once), 5% aqueous citric acid (twice), a saturated aqueous sodium hydrogen carbonate solution (once) and a saturated sodium chloride solution
5. dry with materialThe mixture is dried over sodium sulfate
6. filtrationfiltered
7. customThe mixture is evaporated to dryness in vacuo
8. customdried further under high vacuum