Carbon Dioxide → 4-Chloro-2-fluoro-3-methylbenzoic acid

HRID 1288765Notes

Reaction equation

HRID 1288765 reaction equation
C([Li])CCC.[Cl:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([F:13])[C:8]=1[CH3:14].[C:15](=[O:17])=[O:16]>O1CCCC1>[Cl:6][C:7]1[CH:12]=[CH:11][C:10]([C:15]([OH:17])=[O:16])=[C:9]([F:13])[C:8]=1[CH3:14]

Participants

5

Reactant 3

HCID 280Carbon DioxideHCID 99332-Chloro-6-fluorotolueneHCID 178418339Butyllithium

Product 1

HCID 153137624-Chloro-2-fluoro-3-methylbenzoic acid

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

n-Butyllithium (2.5M in hexane, 100 ml) was added to a cooled solution of 2-chloro-6-fluorotoluene (36.1 g) in dry tetrahydrofuran while maintaining the temperature below -60° C. The mixture was stirred at -78° C. overnight then poured onto solid carbon dioxide pellets. The mixture was stirred and allowed to warm to room temperature. It was acidified to pH 1 and extracted with ether. The organic layer was extracted into aqueous sodium hydroxide solution (2M) and water. The combined aqueous extracts were acidified to pH 1 and the solid formed was filtered off and washed with water and n-hexane to give 4-chloro-2-fluoro-3-methylbenzoic acid (40.35 g) as a white solid, NMR (DMSO-d6) 2.3(d,3H), 7.4(d,1H) 7.7(t,1H).

Workup

  1. temperaturewhile maintaining the temperature below -60° C
  2. stirringThe mixture was stirred
  3. temperatureto warm to room temperature
  4. extractionextracted with ether
  5. extractionThe organic layer was extracted into aqueous sodium hydroxide solution (2M) and water
  6. customthe solid formed
  7. filtrationwas filtered off
  8. washwashed with water and n-hexane

Sources & evidence

ORD record
ord-d8c5544d60ab4361ab9e5ab7f8111139
Source dataset
uspto-grants-1998_05
Patent number
US05747424

Reaction notes

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