2-Amino-1-(4-bromophenyl)ethanone → 3-[2-(4-Bromo-phenyl)-2-oxo-ethylcarbamoyl]-2-aza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester

HRID 79664

Reaction equation

HRID 79664 reaction equation
[NH2:1][CH2:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([Br:11])=[CH:7][CH:6]=1)=[O:4].[C:12]([O:16][C:17]([N:19]1[CH:24]([C:25](O)=[O:26])[CH:23]2[CH2:28][CH:20]1[CH2:21][CH2:22]2)=[O:18])([CH3:15])([CH3:14])[CH3:13].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C>CN(C=O)C.CCOC(C)=O>[C:12]([O:16][C:17]([N:19]1[CH:24]([C:25](=[O:26])[NH:1][CH2:2][C:3]([C:5]2[CH:10]=[CH:9][C:8]([Br:11])=[CH:7][CH:6]=2)=[O:4])[CH:23]2[CH2:28][CH:20]1[CH2:21][CH2:22]2)=[O:18])([CH3:15])([CH3:13])[CH3:14]

Participants

7

Reactant 4

HCID 216392-Amino-1-(4-bromophenyl)ethanoneHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 150563882-(tert-Butoxycarbonyl)-2-azabicyclo[2.2.1]heptane-3-carboxylic acid

Product 1

HCID 596106863-[2-(4-Bromo-phenyl)-2-oxo-ethylcarbamoyl]-2-aza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl esterYield 97.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To the solution of 2-amino-1-(4-bromo-phenyl)-ethanone (HCl salt, 1.0 g, 4 mmol) and 2-aza-bicyclo[2.2.1]heptane-2,3-dicarboxylic acid 2-tert-butyl ester (0.98 g, 4 mmol) in DMF (13 ml) was added HATU (1.64 g, 4.3 mmol), followed by slow addition of diisopropylethylamine (2.2 ml, 12.7 mmol). The mixture was stirred for 4 hours and was diluted with EtOAc. The organic phase was washed with 1 N NaOH solution, water, and brine, and was dried with sodium sulfate. Concentration and purification by flash column chromatography (hexane/EtOAc) gave 3-[2-(4-bromo-phenyl)-2-oxo-ethylcarbarnoyl]-2-aza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester (1.7 g). m/z: 460.9 (M+Na)+.

Workup

  1. washThe organic phase was washed with 1 N NaOH solution, water, and brine
  2. dry with materialwas dried with sodium sulfate
  3. concentrationConcentration and purification by flash column chromatography (hexane/EtOAc)

Sources & evidence

ORD record
ord-75bf9df6f7fc4e5bbcf68be5c05847c6
Source dataset
uspto-grants-2014_09
Patent number
US08841278B2

Linked notes

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