Methanol → 4-Bromo-2-fluoro-benzoic acid methyl ester

HRID 2053709Notes

Reaction equation

HRID 2053709 reaction equation
[Br:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[C:4]([F:11])[CH:3]=1.[CH3:12]O.S(=O)(=O)(O)O>C(OCC)(=O)C>[Br:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([O:8][CH3:12])=[O:7])=[C:4]([F:11])[CH:3]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 1118Sulfuric AcidHCID 3026814-Bromo-2-fluorobenzoic acid

Product 1

HCID 113453114-Bromo-2-fluoro-benzoic acid methyl esterYield 88%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

Combine 4-bromo-2-fluorobenzoic acid (10 g, 45.7 mmol), methanol (100 mL), and concentrated sulfuric acid (5.0 mL). Heat to reflux. After 16 h, cool to room temperature and evaporate in vacuo to afford a white solid. Dissolve the solid in ethyl acetate (about 40 mL), extract with 2×80 mL saturated aqueous sodium bicarbonate and 1×80 mL brine, dry over MgSO4, filter, and evaporate in vacuo to yield 9.32 g (88%) of methyl 4-bromo-2-fluorobenzoate as a white solid. 1H NMR (d6-DMSO, 300 MHz) 8.80 (t, J=8.4 Hz, 1H), 7.72 (dd, J=10.8 Hz, 1.8 Hz, 1H), 7.54 (ddd, J=8.4 Hz, 1.8 Hz, 0.6 Hz, 1H), 3.83 (s, 3H); IR (cm−1, KBr): 3010, 2995, 1723, 1603, 1484, 1438, 1406, 1294, 1277, 1095, 885; Anal calc'd for C8H6BrFO2: C, 41.23; H, 2.60; Found: C, 40.97; H, 2.61.

Workup

  1. temperatureHeat to reflux
  2. customevaporate in vacuo
  3. customto afford a white solid
  4. extractionextract with 2×80 mL saturated aqueous sodium bicarbonate and 1×80 mL brine
  5. dry with materialdry over MgSO4
  6. filtrationfilter
  7. customevaporate in vacuo

Sources & evidence

ORD record
ord-cda6defd2b484bf5b107aed88b98e41c
Source dataset
uspto-grants-2008_02
Patent number
US07326731B2

Reaction notes

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