Methanol → Methyl 2-fluoro-4-hydroxybenzoate

HRID 1662425Notes

Reaction equation

HRID 1662425 reaction equation
[F:1][C:2]1[CH:10]=[C:9]([OH:11])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].S(=O)(=O)(O)O.[CH3:17]O>>[F:1][C:2]1[CH:10]=[C:9]([OH:11])[CH:8]=[CH:7][C:3]=1[C:4]([O:6][CH3:17])=[O:5]

Participants

4

Reactant 3

HCID 887MethanolHCID 1118Sulfuric AcidHCID 27833982-Fluoro-4-hydroxybenzoic Acid

Product 1

HCID 22463192Methyl 2-fluoro-4-hydroxybenzoateYield 85%

Conditions

Temperature
80 °C

Procedure

To a round bottom containing 2-fluoro-4-hydroxybenzoic acid (5.34 g, 34.19 mmol) (commercially available from Matrix Scientific and TCI America) was added a cold solution of MeOH (50 mL) and sulfuric acid (2.0 mL). The mixture was heated to 80° C. and monitored with TLC. After 20.5 hours, the solvent was removed, and the mixture was diluted with diethyl ether. The organic phase was washed carefully two times with saturated. aqueous NaHCO3, once with brine, and then dried over anhydrous sodium sulfate. After filtration, the organic solvent was removed in vacuo to yield 66.43A as a white solid (5.82, 85% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 10.79 (1H, s), 7.75 (1H, t, J=8.8 Hz), 6.69 (1H, dd, J=8.6, 2.3 Hz), 6.62 (1H, dd, J=13.1, 2.2 Hz), 3.78 (3H, s).

Workup

  1. customthe solvent was removed
  2. additionthe mixture was diluted with diethyl ether
  3. washThe organic phase was washed carefully two times with saturated
  4. dry with materialaqueous NaHCO3, once with brine, and then dried over anhydrous sodium sulfate
  5. filtrationAfter filtration
  6. customthe organic solvent was removed in vacuo

Sources & evidence

ORD record
ord-2a01314e220d45f496080c238574c700
Source dataset
uspto-grants-2011_10
Patent number
US08030354B2

Reaction notes

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