Methyl iodide → Benzoic acid, 4-bromo-3-methoxy-2-methyl-, methyl ester

HRID 906124Notes

Reaction equation

HRID 906124 reaction equation
[Br:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([CH3:12])[C:3]=1[OH:13].[C:14](=O)([O-])[O-].[Cs+].[Cs+].IC>CN(C)C=O.C(OCC)(=O)C>[Br:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([CH3:12])[C:3]=1[O:13][CH3:14]

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 10796Cesium carbonateHCID 57700291HCID 57700291, compound

Product 1

HCID 57700263Benzoic acid, 4-bromo-3-methoxy-2-methyl-, methyl esterYield 71%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of methyl 4-bromo-3-hydroxy-2-methylbenzoate (610 mg, 2.5 mmol), cesium carbonate (1.22 g, 3.7 mmol) and iodomethane (162 μl, 2.6 mmol) in dimethylformamide (5 mL) was stirred at room temperature for 15 hours. The mixture was diluted with ethyl acetate, then washed with 5% aqueous lithium chloride then brine and dried over anhydrous sodium sulfate. Filtration and concentration afforded an orange residue, which was purified by silica gel column chromatography. Eluting with 15% diethyl ether in hexane, purified fractions were pooled and concentrated to afford 455 mg, 1.76 mmol (71%) of methyl 4-bromo-2-methyl-3-(methyloxy)benzoate as a colorless residue. 1H NMR (400 MHz, CDCl3): 7.52 (d, 1H), 7.43 (d, 1H), 3.88 (s, 3H), 3.80 (s, 3H), 2.55 (s, 3H). MS (EI) for C10H1BrO3: 260 (MH+).

Workup

  1. washwashed with 5% aqueous lithium chloride
  2. dry with materialbrine and dried over anhydrous sodium sulfate
  3. filtrationFiltration and concentration
  4. customafforded an orange residue, which
  5. customwas purified by silica gel column chromatography
  6. washEluting with 15% diethyl ether in hexane
  7. custompurified fractions
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-a9ceb65ec5cc4696837b4f08398789f6
Source dataset
uspto-grants-2011_09
Patent number
US08012956B2

Reaction notes

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