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

HRID 266577Notes

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

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

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

Sources & evidence

ORD record: ord-b3bbdac69e314cda898534aaab2628d8
Source dataset: uspto-grants-1997_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05650533

Reaction notes

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