Ammonia → 2-Methoxy-6-(trifluoromethyl)phenol

HRID 1757657Notes

Reaction equation

HRID 1757657 reaction equation
C([Li])CCC.CN(C)CCN(C)C.[F:14][C:15]([F:25])([F:24])[C:16]1[CH:17]=[C:18]([O:22][CH3:23])[CH:19]=[CH:20][CH:21]=1.B(OC)(OC)[O:27]C.N>CCCCCC>[CH3:23][O:22][C:18]1[CH:19]=[CH:20][CH:21]=[C:16]([C:15]([F:24])([F:25])[F:14])[C:17]=1[OH:27]

Participants

7

Reactant 5

HCID 222AmmoniaHCID 8037N,N,N',N'-TetramethylethylenediamineHCID 8470Trimethyl borateHCID 966913-(Trifluoromethyl)anisoleHCID 178418339Butyllithium

Product 1

HCID 151333362-Methoxy-6-(trifluoromethyl)phenol

Reagents, catalysts & solvents 1

HCID 8058HexaneSolvent

Conditions

Temperature
-78 °C

Procedure

A solution containing 160 ml of 1.6 molar butyllithium in hexane, 300 ml oftetrahydrofuran and 40 ml of N,N,N',N'-tetramethylethylenediamine was cooled to -78° C. and 43.3 g of 3-trifluoromethylanisole was added with stirring under nitrogen atmosphere. The solution was allowed to warm up to room temperature and cooled then again to -78° C. after which35 ml of trimethyl borate was added. The solution was warmed up to 20° C. and 50 ml of conc. ammonia solution was added. The solvents were evaporated in reduced pressure and to the residue 60 ml of 98-100% formic acid followed with 25 ml of 35% hydrogen peroxide were added. The solution was extracted with ether-petroleum ether (1:1). The organic phasewas separated and the product was extracted with 2.5 N NaOH-solution. The aqueous phase was acidified with hydrochloric acid and the product was extracted in dichloromethane. The solvent was removed for the most part invacuo after which petroleum ether was added. The crystalline product was filtered, yield 8.5 g (18%), m.p. 51°-53° C.

Workup

  1. temperatureto warm up to room temperature
  2. temperaturecooled
  3. temperatureThe solution was warmed up to 20° C.
  4. customThe solvents were evaporated in reduced pressure and to the residue 60 ml of 98-100% formic acid
  5. additionwere added
  6. extractionThe solution was extracted with ether-petroleum ether (1:1)
  7. customThe organic phasewas separated
  8. extractionthe product was extracted with 2.5 N NaOH-solution
  9. extractionthe product was extracted in dichloromethane
  10. customThe solvent was removed for the most part invacuo after which petroleum ether
  11. additionwas added
  12. filtrationThe crystalline product was filtered

Sources & evidence

ORD record
ord-8acec934030a4adcb52de622bcd8c439
Source dataset
uspto-grants-1995_08
Patent number
US05446194

Reaction notes

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