반응 #471141

반응 방정식

(2R)-{[(2R)-2-[(tert-butoxycarbonyl)amino]-2-(2,3-dihydro-1H-inden-2-yl)ethanoyl][(1R)-1-(methoxycarbonyl)-3-methylbutyl]amino}(4-fluorophenyl)ethanoic acid

diisopropylethylamine

phosphorus

2,2,2-trifluoroethylamine

→

(2R)-2-[(3R,6R)-3-(2,3-dihydro-1H-inden-2-yl)-6-isobutyl-2,5-dioxopiperazin-1-yl]-2-(4-fluorophenyl)-N-(2,2,2-trifluoroethyl)ethanamide

용매

N,N-dimethylformamide

반응 조건

후처리

1. 1
   기타before being partitioned between 2M aqueous hydrochloric acid and ethyl acetate
2. 2
   세척The organic layer was washed with saturated aqueous sodium bicarbonate solution and brine
3. 3
   건조before being dried over magnesium sulphate
4. 4
   기타evaporated in vacuo
5. 5
   workup.DISSOLUTIONThe residue was dissolved in 4M hydrogen chloride in dioxane
6. 6
   workup.STIRRINGstirred for 7 hours at room temperature
7. 7
   기타The reagent was removed in vacuo
8. 8
   기타the residue partitioned between ethyl acetate and saturated aqueous sodium bicarbonate solution
9. 9
   세척The separated organic fraction was washed with brine
10. 10
    건조before being dried over magnesium sulphate
11. 11
    기타evaporated in vacuo
12. 12
    기타The crude material was purified by column chromatography (silica)
13. 13
    세척eluting with methanol

실험 절차

A solution of (2R)-{[(2R)-2-[(tert-butoxycarbonyl)amino]-2-(2,3-dihydro-1H-inden-2-yl)ethanoyl][(1R)-1-(methoxycarbonyl)-3-methylbutyl]amino}(4-fluorophenyl)ethanoic acid (73 mg) in N,N-dimethylformamide (2 ml) was sequentially treated with diisopropylethylamine (51 μL), phosphorus, (1-hydroxy-1H-benzotriazolato-O)tri-1-pyrrolidinyl-(T-4)-hexafluorophosphate (80 mg) and then after 2 minutes, 2,2,2-trifluoroethylamine (25 μl). This reaction mixture was stirred for 2 hours before being partitioned between 2M aqueous hydrochloric acid and ethyl acetate. The organic layer was washed with saturated aqueous sodium bicarbonate solution and brine before being dried over magnesium sulphate and evaporated in vacuo. The residue was dissolved in 4M hydrogen chloride in dioxane and stirred for 7 hours at room temperature. The reagent was removed in vacuo and the residue partitioned between ethyl acetate and saturated aqueous sodium bicarbonate solution. The separated organic fraction was washed with brine before being dried over magnesium sulphate and evaporated in vacuo. The crude material was purified by column chromatography (silica) eluting with methanol: dichloromethane (1% to 3%) to furnish ((2R)-2-[(3R,6R)-3-(2,3-dihydro-1H-inden-2-yl)-6-isobutyl-2,5-dioxopiperazin-1-yl]-2-(4-fluorophenyl)-N-(2,2,2-trifluoroethyl)ethanamide (10 mg)

출처