Hydrochloric Acid → 5-Fluoro-2,4-dimethoxybenzoic acid

HRID 2357121Notes

Reaction equation

HRID 2357121 reaction equation
[CH3:1][O:2][C:3]1[CH:10]=[C:9]([O:11][CH3:12])[C:8]([F:13])=[CH:7][C:4]=1[C:5]#N.[OH-:14].[Na+].Cl.C[OH:18]>>[F:13][C:8]1[C:9]([O:11][CH3:12])=[CH:10][C:3]([O:2][CH3:1])=[C:4]([CH:7]=1)[C:5]([OH:18])=[O:14]

Participants

5

Reactant 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 14798Sodium HydroxideHCID 593857025-Fluoro-2,4-dimethoxybenzonitrile

Product 1

HCID 593858915-Fluoro-2,4-dimethoxybenzoic acidYield 93%

Conditions

Temperature
0 °C

Procedure

A solution of 3.1 g (17.2 mmol) of 2,4-dimethoxy-5-fluorobenzonitrile and 100 mL of 6N aqueous sodium hydroxide in 200 mL of methanol was stirred at reflux overnight, cooled to 0° C., acidified to pH 1-2 with 6N aqueous hydrochloric acid, and partitioned between ethyl acetate and brine. The organic extract was dried over Na2SO4, and the solvents were removed in vacuo to give crude 2,4-dimethoxy-5-fluorobenzoic acid as a light-yellow solid. Recrystallization from ethyl acetate and hexane afforded 3.2 g (93%) of 6 as a white solid. 1H NMR (300 MHz, DMSO-d6) δ 12.4 (s, 1H), 7.49 (d, 1H, J=12 Hz), 6.83 (d, 1H, J=7.2 Hz), 3.92 (s, 3H), 3.84 (s, 3H); 13C NMR (75 MHz, DMSO-d6) δ 165.5, 165.5, 156.7, 151.1, 151.0, 146.3, 143.2, 117.9, 117.6, 111.2, 111.1, 99.3, 56.6, 56.4; 19F NMR (282 MHz, DMSO-d6) δ −146.2 (dd, 1F); mass spectrum, calculated for C9H9FO4 (MH+) 201.1, Found 200.9.

Workup

  1. temperatureat reflux overnight
  2. custompartitioned between ethyl acetate and brine
  3. extractionThe organic extract
  4. dry with materialwas dried over Na2SO4
  5. customthe solvents were removed in vacuo
  6. customto give crude 2,4-dimethoxy-5-fluorobenzoic acid as a light-yellow solid
  7. customRecrystallization from ethyl acetate and hexane

Sources & evidence

ORD record
ord-ee60833a195647db9af6c1d8e3658ad9
Source dataset
uspto-grants-2010_07
Patent number
US07759459B2

Reaction notes

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