Water → Methyl 5-bromo-2-[isopropoxycarbonyl-(3-methoxycarbonylpropyl)amino]benzoate

HRID 507019Notes

Reaction equation

HRID 507019 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([NH:12][C:13]([O:15][CH:16]([CH3:18])[CH3:17])=[O:14])=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8].Br[CH2:20][CH2:21][CH2:22][C:23]([O:25][CH3:26])=[O:24].C(=O)([O-])[O-].[Cs+].[Cs+].O>CN(C)C=O>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([N:12]([C:13]([O:15][CH:16]([CH3:18])[CH3:17])=[O:14])[CH2:20][CH2:21][CH2:22][C:23]([O:25][CH3:26])=[O:24])=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8]

Participants

6

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 107604Methyl 4-bromobutyrateHCID 59432449Methyl 5-bromo-2-isopropoxycarbonylaminobenzoate

Product 1

HCID 59432426Methyl 5-bromo-2-[isopropoxycarbonyl-(3-methoxycarbonylpropyl)amino]benzoateYield 89.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Heat a suspension of methyl 5-bromo-2-isopropoxycarbonylaminobenzoate (10.0 g, 31.6 mmol), methyl 4-bromobutyrate (22.9 g, 126 mmol) and cesium carbonate (41.6 g, 126 mmol) in N,N-dimethylformamide (150 mL) under nitrogen at 80° C. for 24 h. Cool the mixture to room temperature and pour into water (200 mL). Extract with ethyl acetate (3×100 mL) and wash the organic extracts with water (3×100 mL) and brine (100 mL). Dry the organic layer over anhydrous sodium sulfate, filter, and remove the solvent under reduced pressure. Chromatograph the residue over silica gel, eluting with hexanes/ethyl acetate (60:40), to provide the title compound as a colorless oil (11.8 g, 89%). 1H NMR (CDCl3, 300 MHz) δ 1.05-1.07 (m, 4H), 1.30-1.32 (m, 2H), 1.89-1.94 (m, 2H), 2.38-2.44 (m, 2H), 3.46-3.60 (m, 1H), 3.65 (s, 3H), 3.68-3.79 (m, 1H), 3.86 (s, 3H), 4.85-5.01 (m, 1H), 7.12 (d, J=8.3 Hz, 1H), 7.62 (dd, J=1.7, 8.4 Hz, 1H), 8.07 (brs, 1H); ESI MS m/z 416 [C17H22BrNO6+H]+.

Workup

  1. temperatureHeat
  2. extractionExtract with ethyl acetate (3×100 mL)
  3. washwash the organic extracts with water (3×100 mL) and brine (100 mL)
  4. dry with materialDry the organic layer over anhydrous sodium sulfate
  5. filtrationfilter
  6. customremove the solvent under reduced pressure
  7. washChromatograph the residue over silica gel, eluting with hexanes/ethyl acetate (60:40)

Sources & evidence

ORD record
ord-4e18d87bb0114adaa499aaf4b472d694
Source dataset
uspto-grants-2010_08
Patent number
US07786108B2

Reaction notes

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