반응 #73897

반응 방정식

(2R)-[(benzyloxycarbonyl)amino](2,3-dihydro-1H-inden-2-yl)ethanoic acid

2-benzyloxyphenylisocyanide

(D)-leucine methyl ester hydrochloride

2,4-difluorobenzaldehyde

methanol

→

(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

용매

triethylamine

반응 조건

후처리

1. 1
   workup.ADDITIONwere sequentially added
2. 2
   workup.WAITThe reaction mixture was left
3. 3
   기타The solvent was removed in vacuo
4. 4
   기타the residue was separated between ethyl acetate (200 ml) and water (200 ml)
5. 5
   세척The organic phase was washed with brine
6. 6
   workup.ADDITIONTo this solution was added palladium on carbon (2.0 g) and acetic acid (10 ml)
7. 7
   여과The mixture was filtered through Celite
8. 8
   세척washed with water (3×100 ml), saturated sodium bicarbonate solution, brine
9. 9
   건조dried over magnesium sulphate
10. 10
    기타The solvent was evaporated in vacuo
11. 11
    기타The crude product was purified by column chromatography (silica)
12. 12
    세척eluting with ethyl acetate

실험 절차

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).

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