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

HRID 495819Notes

Reaction equation

HRID 495819 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.C(OC(=O)N(C)[C@@H](C(=O)N(C)[C@@H](C(=O)NCC1CCCO1)CC1C=CC=CC=1)CC1C2C(=CC=CC=2)C=CC=1)(C)(C)C.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

8

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 3

HCID 6228DimethylformamideSolventHCID 516919Sodium BisulfateSolventHCID 10555137Methyl-((1R)-1-(methyl-((1R)-2-phenyl-1-(((tetrahydrofuran-2-yl)methyl)carbamoyl)ethyl)carbamoyl)-2-(1 naphthyl)ethyl)carbamic acid tert butylesterSolvent

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 1 0% 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)-2phenylethyl)-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-ed1701f633cf48e78e73a1ca576b2b57
Source dataset
uspto-grants-2005_09
Patent number
US06939880B2

Reaction notes

Loading…