Reaktion #62769

Reaktionsgleichung

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

Ausbeute 89.9%

Lösungsmittel

dichloromethane

Reaktionsbedingungen

Aufarbeitung

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

Vorschrift

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##

Quelle