3-Amino-1-propanol → N-((1R)-1-(3-hydroxypropylcarbamoyl)-2-phenylethyl)-N-methylcarbamic acid tert-butylester

HRID 1601979Notes

Reaction equation

HRID 1601979 reaction equation
[NH2:1][CH2:2][CH2:3][CH2:4][OH:5].[C:6]([O:10][C:11]([N:13]([CH3:25])[C@@H:14]([C:22](O)=[O:23])[CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[O:12])([CH3:9])([CH3:8])[CH3:7].O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC>CN(C)C=O.S([O-])(O)(=O)=O.[Na+]>[C:6]([O:10][C:11](=[O:12])[N:13]([C@@H:14]([C:22](=[O:23])[NH:1][CH2:2][CH2:3][CH2:4][OH:5])[CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[CH3:25])([CH3:7])([CH3:9])[CH3:8]

Participants

7

Reactant 4

HCID 90863-Amino-1-propanolHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 7015127N-Boc-N-methyl-D-phenylalanine

Product 1

HCID 54054214N-((1R)-1-(3-hydroxypropylcarbamoyl)-2-phenylethyl)-N-methylcarbamic acid tert-butylesterYield 64.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 516919Sodium BisulfateSolvent

Procedure

3-Aminopropan-1-ol (0.39 mL, 5.12 mmol) was added at room temperature to a solution of N-tert-butoxycarbonyl-N-methyl-D-phenylalanine (1.30 g, 4.65 mmol) in N,N-dimethylformamide (40 mL). 1-Hydroxybenzotriazole monohydrate (0.63 g, 4.65 mmol) and N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (0.89 g, 4.65 mmol) were added successively. The reaction mixture was stirred for 22 h at room temperature. It was diluted with 10% sodium hydrogensulfate solution (300 mL) and extracted with ethyl acetate (4×100 mL). The combined organic layers were dried over magnesium sulfate. The solvent was removed in vacuo and the crude product was purified by flash chromatography on silica (45 g) with dichloromethane/methanol (10:1) to give 1.01 g of N-((1R)-1-(3-hydroxypropylcarbamoyl)-2-phenylethyl)-N-methylcarbamic acid tert-butylester.

Workup

  1. extractionextracted with ethyl acetate (4×100 mL)
  2. dry with materialThe combined organic layers were dried over magnesium sulfate
  3. customThe solvent was removed in vacuo
  4. customthe crude product was purified by flash chromatography on silica (45 g) with dichloromethane/methanol (10:1)

Sources & evidence

ORD record
ord-96c97f0e3f344e879854434ed0f075b3
Source dataset
uspto-grants-1999_11
Patent number
US05977178

Reaction notes

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