반응 #62769

반응 방정식

1-[2-chloro-3-(2,4-dichlorophenyl)-3-oxo-2-phenylpropyl]-N-[(1,1-dimethylethoxy)carbonyl]-L-histidine

N-methylmorpholine

1-hydroxybenzotriazole hydrate

L-alanine 1,1-dimethylethyl ester hydrochloride

N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride

→

N-[1-[2-chloro-3-(2,4-dichlorophenyl)-3-oxo-2-phenylpropyl]-N-[(1,1-dimethylethoxy)carbonyl]-L-histidyl]-L-alanine 1,1-dimethylethyl ester

수율 89.9%

용매

dichloromethane

반응 조건

후처리

1. 1
   농축concentrated under reduced pressure
2. 2
   기타to yield a residue which
3. 3
   기타was partitioned between ethyl acetate and water
4. 4
   세척The organic phase was washed with saturated aqueous sodium hydrogen carbonate
5. 5
   건조brine and dried over anhydrous magnesium sulphate
6. 6
   기타The solvent was removed under reduced pressure
7. 7
   기타to yield a foam which
8. 8
   기타was chromatographed on silica gel eluting with methanol/dichloromethane (1:24)

실험 절차

To a stirred mixture of 1-[2-chloro-3-(2,4-dichlorophenyl)-3-oxo-2-phenylpropyl]-N-[(1,1-dimethylethoxy)carbonyl]-L-histidine (1.14 g), N-methylmorpholine (461 μl), 1-hydroxybenzotriazole hydrate (277 mg) and L-alanine 1,1-dimethylethyl ester hydrochloride (364 mg) in dichloromethane (30 ml) was added N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (422 mg). The resulting mixture was stirred for 18 hours, and concentrated under reduced pressure to yield a residue which was partitioned between ethyl acetate and water. The organic phase was washed with saturated aqueous sodium hydrogen carbonate and then brine and dried over anhydrous magnesium sulphate. The solvent was removed under reduced pressure to yield a foam which was chromatographed on silica gel eluting with methanol/dichloromethane (1:24) to yield N-[1-[2-chloro-3-(2,4-dichlorophenyl)-3-oxo-2-phenylpropyl]-N-[(1,1-dimethylethoxy)carbonyl]-L-histidyl]-L-alanine 1,1-dimethylethyl ester as a white foam (1.25 g), and as a mixture of diastereoisomers, m.p. 85-90° C. (decomp), (Found: C, 55.57; H, 5.51; N, 7.86%; C33H39Cl3N4O6.H2O requires C, 55.66; H, 5.80; N, 7.87%), having the formula: ##STR35##

출처