反应详情

To a solution of (D)-leucine methyl ester hydrochloride (1.45 g) in methanol (10 ml) was added triethylamine (1.12 ml) and 2,4-difluorobenzaldehyde (0.875 ml). The mixture was stirred for 3 days before (2R)-[(benzyloxycarbonyl)amino](2,3-dihydro-1H-inden-2-yl)ethanoic acid (2.6 g) and 2-benzyloxyphenylisocyanide (1.76 g) were sequentially added. The reaction mixture was left to stand for 24 hours. The solvent was removed in vacuo and the residue was separated between ethyl acetate (200 ml) and water (200 ml). The organic phase was washed with brine. To this solution was added palladium on carbon (2.0 g) and acetic acid (10 ml) and the reaction mixture was stirred under an atmosphere of hydrogen for 2 hours. The mixture was filtered through Celite and washed with water (3×100 ml), saturated sodium bicarbonate solution, brine and dried over magnesium sulphate. The solvent was evaporated in vacuo. The crude product was purified by column chromatography (silica) eluting with ethyl acetate:cyclohexane (50% to 66%) to give (2RS)-2-(2,4-difluorophenyl)-2-[(3R,6R)-3-(2,3-dihydro-1H-inden-2-yl)-6-isobutyl-2,5-dioxopiperazin-1-yl]-N-(2-hydroxyphenyl)ethanamide (2.0 g).

1. additionwere sequentially added
2. waitThe reaction mixture was left
3. customThe solvent was removed in vacuo
4. customthe residue was separated between ethyl acetate (200 ml) and water (200 ml)
5. washThe organic phase was washed with brine
6. additionTo this solution was added palladium on carbon (2.0 g) and acetic acid (10 ml)
7. filtrationThe mixture was filtered through Celite
8. washwashed with water (3×100 ml), saturated sodium bicarbonate solution, brine
9. dry with materialdried over magnesium sulphate
10. customThe solvent was evaporated in vacuo
11. customThe crude product was purified by column chromatography (silica)
12. washeluting with ethyl acetate