Dicyclohexylcarbodiimide → HCID 22879396, compound

HRID 1290019Notes

Reaction equation

HRID 1290019 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH:12]=[C:11]([CH2:13][C@H:14]([NH:18][C:19](=[O:36])[C@@H:20]([CH2:28][S:29]([C:32]([CH3:35])([CH3:34])[CH3:33])(=[O:31])=[O:30])[CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[C:15]([OH:17])=O)[N:10]=[CH:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH2:37][C@@H:38]([CH2:46][CH:47]1[CH2:52][CH2:51][CH2:50][CH2:49][CH2:48]1)[C@@H:39]([OH:45])[C@H:40]([CH:42]1[CH2:44][CH2:43]1)[OH:41].C1(N=C=NC2CCCCC2)CCCCC1>C(OCC)(=O)C.ON1C(=O)CCC1=O>[C:32]([S:29]([CH2:28][C@@H:20]([CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[C:19]([NH:18][C@H:14]([C:15](=[O:17])[NH:37][C@@H:38]([CH2:46][CH:47]1[CH2:52][CH2:51][CH2:50][CH2:49][CH2:48]1)[C@@H:39]([OH:45])[C@H:40]([CH:42]1[CH2:44][CH2:43]1)[OH:41])[CH2:13][C:11]1[N:10]=[CH:9][N:8]([C:6]([O:5][C:1]([CH3:3])([CH3:4])[CH3:2])=[O:7])[CH:12]=1)=[O:36])(=[O:30])=[O:31])([CH3:35])([CH3:33])[CH3:34]

Participants

6

Reactant 3

HCID 10868DicyclohexylcarbodiimideHCID 14930738(1S,2R,3S)-3-amino-4-cyclohexyl-1-cyclopropyl-1,2-butanediolHCID 22862631HCID 22862631, compound

Product 1

HCID 22879396HCID 22879396, compoundYield 87.2%

Reagents, catalysts & solvents 2

HCID 80170N-HydroxysuccinimideCatalystHCID 8857Ethyl AcetateSolvent2×

Procedure

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.

Workup

  1. filtrationThe solid (dicyclohexylurea) was filtered off
  2. additionthe filtrate was treated
  3. stirringwhile stirring firstly with 68 ml of deionized water
  4. filtrationAfter one hour at 0° the crystallizate was filtered off under suction
  5. customtriturated in methanol at 20°
  6. temperatureThe suspension was cooled to -15°
  7. filtrationthe product was filtered off

Sources & evidence

ORD record
ord-96b5aa879ad2437a97b3de407854ed79
Source dataset
uspto-grants-1998_05
Patent number
US05750649

Reaction notes

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