Methyl iodide → Benzoic acid, 3-fluoro-5-methyl-, methyl ester

HRID 1426290Notes

Reaction equation

HRID 1426290 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([CH3:11])[CH:10]=1)[C:5]([OH:7])=[O:6].[C:12](=O)([O-])[O-].[K+].[K+].CI>CC(C)=O>[F:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([CH3:11])[CH:10]=1)[C:5]([O:7][CH3:12])=[O:6]

Participants

5

Reactant 3

HCID 6328Methyl iodide2×HCID 11430Potassium CarbonateHCID 27784473-Fluoro-5-methylbenzoic acid

Product 1

HCID 44203100Benzoic acid, 3-fluoro-5-methyl-, methyl ester

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Conditions

Temperature
65 °C

Procedure

To a solution of 3-fluoro-5-methylbenzoic acid (1.50 g, 9.73 mmol, Oakwood) in Acetone (40 mL) was added Potassium carbonate (1.34 g, 9.73 mmol) followed by Methyl iodide (0.73 mL, 12 mmol). The reaction mixture was heated to 65° C. for 1 hour, heating discontinued and stirred overnight, then heating resumed at that temperature for a further 2 hours. Additional Methyl iodide (0.5 mL, 8 mmol) was added and heating was continued for 6 hours. Solids were removed by filtration and acetone was removed in vacuo. The residue was partitioned between 1N NaOH and ethyl acetate. The aqueous portion was extracted with a further two portions of ethyl acetate. The combined extracts were washed with brine, then dried over sodium sulfate, decanted and concentrated. The product so obtained was used without further purification (1.64 g, 100%). 1H NMR (300 MHz, CDCl3): δ 7.66-7.63 (m, 1H), 7.51 (d, 1H), 7.10-7.04 (m, 1H), 3.91 (s, 3H), 2.40 (s, 3H).

Workup

  1. temperatureheating
  2. temperatureheating
  3. waitresumed at that temperature for a further 2 hours
  4. temperatureheating
  5. waitwas continued for 6 hours
  6. customSolids were removed by filtration and acetone
  7. customwas removed in vacuo
  8. customThe residue was partitioned between 1N NaOH and ethyl acetate
  9. extractionThe aqueous portion was extracted with a further two portions of ethyl acetate
  10. washThe combined extracts were washed with brine
  11. dry with materialdried over sodium sulfate
  12. customdecanted
  13. concentrationconcentrated
  14. customThe product so obtained
  15. customwas used without further purification (1.64 g, 100%)

Sources & evidence

ORD record
ord-2ea7cfbc03cd41209ab6f140629df780
Source dataset
uspto-grants-2015_01
Patent number
US08933085B2

Reaction notes

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