Reaktion #1377201

Reaktionsgleichung

(S)-1-(t-butoxycarbonyl)-α-[(S)-α-[(t-butylsulphonyl)methyl]hydrocinnamamido]imidazole-4-propionic acid

(1S,2R,3S)-3-amino-4-cyclohexyl-1-cyclopropyl-butane-1,2-diol

dicyclohexylcarbodiimide

→

t-butyl 4-[(S)-2-[(S)-2-t-butanesulphonylmethyl-3-phenylpropionylamino]-2-[(1S,2R,3S)-1-cyclohexylmethyl-3-cyclopropyl-2,3-dihydroxy-propylcarbamoyl]ethyl]-1H-imidazole-1-carboxylate

Ausbeute 87.2%

Lösungsmittel

ethyl acetate

ethyl acetate

Reaktionsbedingungen

Aufarbeitung

1. 1
   FiltrationThe solid (dicyclohexylurea) was filtered off
2. 2
   workup.ADDITIONthe filtrate was treated
3. 3
   workup.STIRRINGwhile stirring firstly with 68 ml of deionized water
4. 4
   FiltrationAfter one hour at 0° the crystallizate was filtered off under suction
5. 5
   Sonstigetriturated in methanol at 20°
6. 6
   TemperaturThe suspension was cooled to -15°
7. 7
   Filtrationthe product was filtered off

Vorschrift

89 g (170 mmol) of (S)-1-(t-butoxycarbonyl)-α-[(S)-α-[(t-butylsulphonyl)methyl]hydrocinnamamido]imidazole-4-propionic acid, 1 g (8.5 mmol) of N-hydroxysuccinimide, 35.5 g (155 mmol) of (1S,2R,3S)-3-amino-4-cyclohexyl-1-cyclopropyl-butane-1,2-diol and 800 ml of ethyl acetate were stirred at 20°. A solution of 37 g (178 mmol) of dicyclohexylcarbodiimide in 110 ml of ethyl acetate was added within 10 minutes. The reaction had finished after stirring at 20° for 17 hours. The solid (dicyclohexylurea) was filtered off and the filtrate was treated while stirring firstly with 68 ml of deionized water and then with 1100 ml of hexane. After one hour at 0° the crystallizate was filtered off under suction and triturated in methanol at 20°. The suspension was cooled to -15° and the product was filtered off. 98.8 g (86%) of t-butyl 4-[(S)-2-[(S)-2-t-butanesulphonylmethyl-3-phenylpropionylamino]-2-[(1S,2R,3S)-1-cyclohexylmethyl-3-cyclopropyl-2,3-dihydroxy-propylcarbamoyl]ethyl]-1H-imidazole-1-carboxylate were obtained.

Quelle