1-Hydroxybenzotriazole → 2-((2S,3S)-2-tert-butoxycarbonylamino-3-phenyl-butyrylamino)-thiazole-4-carboxylic acid methyl ester

HRID 32827

Reaction equation

HRID 32827 reaction equation
[CH3:1][O:2][C:3]([C:5]1[N:6]=[C:7]([NH2:10])[S:8][CH:9]=1)=[O:4].[C:11]([O:15][C:16]([NH:18][C@@H:19]([C@H:23]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[CH3:24])[C:20](O)=[O:21])=[O:17])([CH3:14])([CH3:13])[CH3:12].ON1C2C=CC=CC=2N=N1>CN(C)C=O.C(OCC)(=O)C>[CH3:1][O:2][C:3]([C:5]1[N:6]=[C:7]([NH:10][C:20](=[O:21])[C@@H:19]([NH:18][C:16]([O:15][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:17])[C@H:23]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH3:24])[S:8][CH:9]=1)=[O:4]

Participants

6

Reactant 3

HCID 757711-HydroxybenzotriazoleHCID 840099Methyl 2-amino-1,3-thiazole-4-carboxylateHCID 7021178(2S,3S)-2-((tert-Butoxycarbonyl)amino)-3-phenylbutanoic acid

Product 1

HCID 866033892-((2S,3S)-2-tert-butoxycarbonylamino-3-phenyl-butyrylamino)-thiazole-4-carboxylic acid methyl esterYield 43%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

2-Amino-thiazole-4-carboxylic acid methyl ester (0.57 g, 3.62 mmol) and (2S,3S)-2-tert-butoxycarbonylamino-3-phenyl-butyric acid (Acros) (1.01 g, 3.62 mmol), 1-hydroxybenzotriazole and (0.59 g, 4.34 mmol) and O-benzeotrazol-1-yl-N,N,N′,N′-tetramethyluroniumhexaflurorophosphate (1.65 g, 4.34 mmol) in N,N-dimethylformamide (8 mL) were stirred at ambient temperature for 24 hours. The mixture was diluted with ethyl acetate, washed with water, brine and dried (magnesium sulfate). Evaporation of the solvents and chromatography of the residue over silica gel gradient eluted with 0.2-1.5% methanol in dichloromethane gave 2-((2S,3S)-2-tert-butoxycarbonylamino-3-phenyl-butyrylamino)-thiazole-4-carboxylic acid methyl ester (0.65 g, 43%).

Workup

  1. washwashed with water, brine
  2. dry with materialdried (magnesium sulfate)
  3. customEvaporation of the solvents and chromatography of the residue over silica gel gradient
  4. washeluted with 0.2-1.5% methanol in dichloromethane

Sources & evidence

ORD record
ord-a5954397d2c34521831f97ca2fbf10e4
Source dataset
uspto-grants-2008_09
Patent number
US07427635B2

Linked notes

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