Cesium carbonate → Methyl 4-bromo-2-[isopropoxycarbonyl-(3-methoxycarbonylpropyl)amino]benzoate

HRID 2353872Notes

Reaction equation

HRID 2353872 reaction equation
[Br:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([NH:12][C:13]([O:15][CH:16]([CH3:18])[CH3:17])=[O:14])[CH:3]=1.I[CH2:20][CH2:21][CH2:22][C:23]([O:25][CH3:26])=[O:24].C(=O)([O-])[O-].[Cs+].[Cs+].[Cl-].[NH4+]>CN(C)C=O>[Br:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([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])[CH:3]=1

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 25517Ammonium ChlorideHCID 547991Methyl 4-iodobutanoateHCID 68680673Methyl 4-bromo-2-isopropoxycarbonylaminobenzoate

Product 1

HCID 68678592Methyl 4-bromo-2-[isopropoxycarbonyl-(3-methoxycarbonylpropyl)amino]benzoateYield 63%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Heat a suspension of methyl 4-bromo-2-isopropoxycarbonylaminobenzoate (19.2 g, 60.7 mmol), methyl 4-iodobutyrate (16.4 mL, 121 mmol) and cesium carbonate (39.6 g, 121 mmol) in N,N-dimethylformamide (240 mL) under nitrogen at 80° C. for 24 h. Cool the mixture to room temperature and pour into a saturated ammonium chloride solution (500 mL) and extract with ethyl acetate (3×200 mL). Combine the organic extracts and wash with water (2×400 mL), brine (100 mL), then dry the solution over sodium sulfate, filter and remove the solvent under reduced pressure. Purify the residue using chromatography on silica gel, eluting with hexanes/ethyl acetate (60:40), to provide the title compound as an orange oil (15.9 g, 63%): APCI MS 416 (M+H

Workup

  1. temperatureHeat
  2. extractionextract with ethyl acetate (3×200 mL)
  3. washCombine the organic extracts and wash with water (2×400 mL), brine (100 mL)
  4. dry with materialdry the solution over sodium sulfate
  5. filtrationfilter
  6. customremove the solvent under reduced pressure
  7. customPurify the residue
  8. washeluting with hexanes/ethyl acetate (60:40)

Sources & evidence

ORD record
ord-3dff4a1c4c2e4d78a3e541bd590973e3
Source dataset
uspto-grants-2010_07
Patent number
US07749992B2

Reaction notes

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