3-(Trifluoromethyl)anisole → 2-Methoxy-6-(trifluoromethyl)benzoic acid

HRID 619973Notes

Reaction equation

HRID 619973 reaction equation
[F:1][C:2]([F:12])([F:11])[C:3]1[CH:4]=[C:5]([O:9][CH3:10])[CH:6]=[CH:7][CH:8]=1.C([Li])CCC.[C:18](=[O:20])=[O:19].CCOCC>O1CCCC1.O>[CH3:10][O:9][C:5]1[C:4]([C:18]([OH:20])=[O:19])=[C:3]([C:2]([F:11])([F:12])[F:1])[CH:8]=[CH:7][CH:6]=1

Participants

6

Reactant 3

HCID 966913-(Trifluoromethyl)anisoleHCID 86742199Dry ice diethyl etherHCID 178418339Butyllithium

Product 1

HCID 150175332-Methoxy-6-(trifluoromethyl)benzoic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 3-trifluoromethylanisol (50.0 g, 0.28 mole) in tetrahydrofuran was cooled to -78° C. under nitrogen atmosphere with stirring. To this solution was added n-butyl lithium (114 ml of 2.5M, 0.28 mole), dropwise at such a rate that the temperature did not exceed -65° C. When the addition was complete, the mixture was stirred at -78° C. for three hours. The mixture was then poured over a slurry of dry ice/ether and allowed to come to room temperature. The solvent was removed under reduced pressure to give a white solid. This solid was dissolved in a minimum amount of water, extracted with diethyl ether (2×100 ml) and the aqueous phase was acidified to pH 2 with dilute hydrochloric acid. An oil formed and was extracted with diethyl ether, washed several times with water and dried over magnesium sulfate. The solvent was removed to give 45.6 g (74 percent of theory) of the title compound as a white solid of m.p. 129°-130° C.

Workup

  1. customdid not exceed -65° C
  2. additionWhen the addition
  3. stirringthe mixture was stirred at -78° C. for three hours
  4. customto come to room temperature
  5. customThe solvent was removed under reduced pressure
  6. customto give a white solid
  7. extractionextracted with diethyl ether (2×100 ml)
  8. customAn oil formed
  9. extractionwas extracted with diethyl ether
  10. washwashed several times with water
  11. dry with materialdried over magnesium sulfate
  12. customThe solvent was removed

Sources & evidence

ORD record
ord-dd2e247d1d9b4cfebba97e94e788e6a0
Source dataset
uspto-grants-1989_04
Patent number
US04818273

Reaction notes

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