反应详情

A solution of diisopropylethylamine (8.7 ml., 50 mmole) in tetrahydrofuran (50 ml.) is added dropwise to a mixture of N-[(1,1-dimethylethoxy) carbonyl]-L-phenylalanine (13.265 g., 50 mmole), L-leucine, methyl ester (9.085 g., 50 mmole) and 1-hydroxybenzotriazole hydrate (7.65 g., 50 mmole) in tetrahydrofuran (100 ml.) at 0°. This is followed by the addition of dicylcohexylcarbodiimide (10.315 g., 50 mmole). The reaction is stirred at 0°for 2 hours and left stirring overnight at room temperature. The nexy day, the precipitated dicyclohexyl urea is filtered off, the solvents are stirred down and the residue is diluted with ethyl acetate (200 ml.). The organic solution is washed sequentially with saturated aqueous sodium bicarbonate solution (2×100 ml.) and saturated aqueous sodium chloride (2×100 ml.), dried over sodium sulfate, filtered, and concentrated to give crude product. Crystallization from ethyl ether gives 7.05 g. of pure product. Concentration of the mother liquor solutions gives 4.57 g. of crystalline product. An additional 1.35 g. of product is obtained by chromatographic purification of the crude product obtained from the left-over mother liquors (40 g. silica gel, eluting with 4:1 hexane:ethyl acetate). Thus, a total of 12.96 g. of N-[N-[(1,1 -dimethylethoxy)carbonyl]-L-leucine, methyl ester is obtained;

1. waitleft
2. stirringstirring overnight at room temperature
3. filtrationThe nexy day, the precipitated dicyclohexyl urea is filtered off
4. stirringthe solvents are stirred down
5. additionthe residue is diluted with ethyl acetate (200 ml.)
6. washThe organic solution is washed sequentially with saturated aqueous sodium bicarbonate solution (2×100 ml.) and saturated aqueous sodium chloride (2×100 ml.)
7. dry with materialdried over sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated
10. customto give crude product
11. customCrystallization from ethyl ether
12. customgives 7.05 g
13. customConcentration of the mother liquor solutions gives 4.57 g
14. customof product is obtained by chromatographic purification of the crude product
15. customobtained from the
16. washleft-over mother liquors (40 g. silica gel, eluting with 4:1 hexane:ethyl acetate)