Dicyclohexylcarbodiimide → HCID 70058166, compound

HRID 1080919Notes

Reaction equation

HRID 1080919 reaction equation
[NH2:1][C@@H:2]([CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[C@H:3]([OH:18])[CH2:4][C@@H:5]1[CH2:10][CH2:9][CH2:8][CH2:7][C@H:6]1[C:11]([NH:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12].[CH2:26]([O:33][C:34]([N:36](C#N)[C@H:37]([C:39]([OH:41])=O)[CH3:38])=[O:35])[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.O.OC1C2N=N[NH:51][C:50]=2C=CC=1.C1(N=C=NC2CCCCC2)CCCCC1>ClCCl.CN(C)C=O>[CH2:26]([O:33][C:34]([NH:36][C@H:37]([C:39]([NH:1][C@@H:2]([CH2:19][C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1)[C@H:3]([OH:18])[CH2:4][C@@H:5]1[CH2:10][CH2:9][CH2:8][CH2:7][C@H:6]1[C:11]([NH:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])=[O:41])[CH2:38][C:50]#[N:51])=[O:35])[C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1

Participants

7

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 53758257HCID 53758257, compoundHCID 70049550HCID 70049550, compoundHCID 178526939HCID 178526939, compound

Product 1

HCID 70058166HCID 70058166, compoundYield 51.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of 90mg (0.26 mmol) of 2(S)-[3(S)-amino-2(R)-hydroxy-4-phenylbutyl]-N-tert.butyl-1(R)-cyclohexanecarboxamide in 4 ml of dichloromethane was added to a mixture of 65 mg (0.26 mmol) of N-benzyloxycarbonyl-cyano-L-alanine, 35 mg (0.23 mmol) of hydroxybenzotriazole hydrate and 54 mg (0.26 mmol) of dicyclohexylcarbodiimide in 2 ml of dimethylformamide. The mixture-was stirred under nitrogen at room temperature for 18 hours and then filtered. The filtrate was evaporated and the residue was partitioned between 25 ml of ethyl acetate and 10 ml of saturated aqueous sodium hydrogen carbonate solution. The organic layer was dried over anhydrous magnesium sulphate and evaporated. The crude product was chromatographed on a column of silica gel using 3% methanol in dichloromethane for the elution and the product was purified further by crystallization from a mixture of 1 ml of dichloromethane and 10 ml of hexane. There were obtained 68 mg of 2(S)-[3(S)-[[N-(benzyloxycarbonyl)-3-cyano-L-alanyl]amino]-2(R)-hydroxy-4-phenylbutyl]-N-tert.butyl-1(R)-cyclohexanecarboxamide as a white solid; MS m/e 577 [M+H]+.

Workup

  1. filtrationfiltered
  2. customThe filtrate was evaporated
  3. customthe residue was partitioned between 25 ml of ethyl acetate and 10 ml of saturated aqueous sodium hydrogen carbonate solution
  4. dry with materialThe organic layer was dried over anhydrous magnesium sulphate
  5. customevaporated
  6. customThe crude product was chromatographed on a column of silica gel using 3% methanol in dichloromethane for the elution
  7. customthe product was purified further by crystallization from a mixture of 1 ml of dichloromethane and 10 ml of hexane

Sources & evidence

ORD record
ord-693b5c0b536e4693bf4f224dd1c28134
Source dataset
uspto-grants-1996_12
Patent number
US05583248

Reaction notes

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