4-Methylmorpholine → tert-butyl N-[1-benzyl-3-[[(2S)-2-(benzyloxycarbonylamino)-3-methyl-butanoyl]amino]-2-hydroxy-4-phenyl-butyl]carbamate

HRID 847603Notes

Reaction equation

HRID 847603 reaction equation
[NH:1]([C:9]([O:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[O:10])[C@H:2]([C:6]([OH:8])=O)[CH:3]([CH3:5])[CH3:4].[NH2:19][CH:20]([CH2:39][C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1)[CH:21]([OH:38])[CH:22]([NH:30][C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.ON1C2C=CC=CC=2N=N1.CN1CCOCC1.Cl.C(N=C=NCCCN(C)C)C>CN(C)C=O.C(OCC)(=O)C>[C:34]([O:33][C:31]([NH:30][CH:22]([CH:21]([OH:38])[CH:20]([NH:19][C:6](=[O:8])[C@H:2]([CH:3]([CH3:4])[CH3:5])[NH:1][C:9]([O:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[O:10])[CH2:39][C:40]1[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=1)[CH2:23][C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1)=[O:32])([CH3:37])([CH3:35])[CH3:36]

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 726987N-Carbobenzoxy-L-valineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 147043774-Amino-2-(t-butyloxycarbonylamino)-1,5-diphenyl-3-hydroxypentane

Product 1

HCID 3011021tert-butyl N-[1-benzyl-3-[[(2S)-2-(benzyloxycarbonylamino)-3-methyl-butanoyl]amino]-2-hydroxy-4-phenyl-butyl]carbamateYield 94.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 39 mg (0.16 mmol) of Cbz-Val-OH, 52 mg (0.14 mmol) of the resultant compound of Example 11, and 23 mg (0.17 mmol) of 1-hydroxybenzotriazole in 2 ml of dimethylformamide was treated with 0.019 ml (0.17 mmol) of 4-methylmorpholine, cooled to 0° C., and treated with 33 mg (0.17 mmol) of N-ethyl-N'-(dimethylaminopropyl)-carbodiimide hydrochloride. After being stirred at ambient temperature overnight, the solution was diluted with ethyl acetate, washed sequentially with 10% citric acid, water, and aqueous NaHCO3, dried over Na2SO4, and concentrated in vacuo. Separation of the desired compounds by flash chromatography using methanol in chloroform gave 80 mg (95%) of the desired compound (Rf 0.40, 10% methanol in chloroform) as a white solid, m.p. 187°-187.5° C. Mass spectrum (M+H)+ =604.

Workup

  1. washwashed sequentially with 10% citric acid, water, and aqueous NaHCO3
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated in vacuo
  4. customSeparation of the desired compounds by flash chromatography

Sources & evidence

ORD record
ord-347a4931554c49da9da29b0a95f1757a
Source dataset
uspto-grants-1992_08
Patent number
US05142056

Reaction notes

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