Methane → 1-[2-Hydroxy-4-(trifluoromethyl)phenyl]ethan-1-one

HRID 1911269Notes

Reaction equation

HRID 1911269 reaction equation
[OH:1][C:2]1[CH:10]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.[CH3:15][Li].C.Cl>CCOCC.CCOC(C)=O.C1COCC1>[OH:1][C:2]1[CH:10]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:8]=[CH:7][C:3]=1[C:4](=[O:6])[CH3:15]

Participants

8

Reactant 4

HCID 297MethaneHCID 313Hydrochloric AcidHCID 1645782-Hydroxy-4-(trifluoromethyl)benzoic acidHCID 178418348HCID 178418348, compound2×

Product 1

HCID 154464491-[2-Hydroxy-4-(trifluoromethyl)phenyl]ethan-1-one

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

A solution of 2-hydroxy-4-(trifluoromethyl)benzoic acid (10.0 g, 48.5 mmol) and THF (100 mL) was cooled to <5° C. (internal temperature) and methyllithium (95 mL of a 1.6M solution in Et2O, 152 mmol) was added, keeping the internal temperature≦20° C. (slow addition, methane generation). Following methyllithium addition, the solution was warmed to ambient temperature and stirred for 1 h. The solution was then re-cooled to 10° C. and treated carefully with EtOAc (100 mL) and 2N HCl (100 mL). The reaction mixture was further diluted with EtOAc (100 mL) then washed with water (100 mL) and brine (20 mL). The organic portion was dried (Na2SO4), filtered, and concentrated to give 1-(2-hydroxy-4-(trifluoromethyl)phenyl)ethanone (10.3 g) which was used without further purification.

Workup

  1. additionwas added
  2. temperatureThe solution was then re-cooled to 10° C.
  3. washthen washed with water (100 mL) and brine (20 mL)
  4. dry with materialThe organic portion was dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-6b72b674de6c4a9498d51e19a98ad655
Source dataset
uspto-grants-2013_12
Patent number
US08604053B2

Reaction notes

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