Carbon Dioxide → 6-Bromo-2-fluoro-3-methylbenzoic acid

HRID 2052763Notes

Reaction equation

HRID 2052763 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[C:4]([F:9])[CH:3]=1.[Li+].CC([N-]C(C)C)C.[C:18](=[O:20])=[O:19].Cl>C1COCC1>[Br:1][C:2]1[C:3]([C:18]([OH:20])=[O:19])=[C:4]([F:9])[C:5]([CH3:8])=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 280Carbon DioxideHCID 313Hydrochloric AcidHCID 1710404-Bromo-2-fluorotolueneHCID 2724682Lithium diisopropylamide

Product 1

HCID 586874916-Bromo-2-fluoro-3-methylbenzoic acidYield 49.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

50 ml (0.385 mol) of 4-bromo-2-fluorotoluene were dissolved in 750 ml of THF, and 231 ml (0.462 mol) of a 2 M solution of LDA in THF were added dropwise at −70° C. After 70 minutes, 37.2 g (0.846 mol) of carbon dioxide were passed in, and the batch was allowed to thaw. After acidification using conc. hydrochloric acid, the solution was extracted with MTB ether, and the combined organic phases were washed with water, dried over sodium sulfate and evaporated under reduced pressure. Crystallisation of the crude product from 1-chlorobutane gave 44.1 g (49%) of 6-bromo-2-fluoro-3-methylbenzoic acid as white crystals.

Workup

  1. extractionthe solution was extracted with MTB ether
  2. washthe combined organic phases were washed with water
  3. dry with materialdried over sodium sulfate
  4. customevaporated under reduced pressure
  5. customCrystallisation of the crude product from 1-chlorobutane

Sources & evidence

ORD record
ord-7306bfdfafb64beabaa94c82bf0644ee
Source dataset
uspto-grants-2008_02
Patent number
US07326447B2

Reaction notes

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