Benzyl Alcohol → 4-Methoxy-1-(phenylmethoxy)-2-(trifluoromethyl)benzene

HRID 1406368Notes

Reaction equation

HRID 1406368 reaction equation
[CH2:1]([OH:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].F[C:12]1[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][C:13]=1[C:20]([F:23])([F:22])[F:21]>CN1C(=O)CCC1.O>[CH2:1]([O:8][C:12]1[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][C:13]=1[C:20]([F:21])([F:22])[F:23])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 244Benzyl AlcoholHCID 24758Sodium hydrideHCID 27747764-Fluoro-3-(trifluoromethyl)anisole

Product 1

HCID 118585814-Methoxy-1-(phenylmethoxy)-2-(trifluoromethyl)benzene

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent2×

Procedure

18 g (166.67 mmol) of benzylalcohol was slowly added to a solution of 6.7 g (167.50 mmol) of sodium hydride in 148 mL NMP. The reaction mixture was stirred for 30 min at RT, then a solution of 27 g (139.09 mmol) of 1-fluoro-4-methoxy-2-trifluoromethyl-benzene in 515 mL NMP was added, and this was stirred for 30 min at RT and for 2 h at 100° C. After cooling to RT the mixture was diluted with water and extracted with ethyl acetate, the organic phase was washed with saturated sodium chloride solution, dried on sodium sulphate and evaporated down. The residue was purified by chromatography (silica gel, petroleum ether/ethyl acetate).

Workup

  1. stirringthis was stirred for 30 min at RT and for 2 h at 100° C
  2. temperatureAfter cooling to RT the mixture
  3. extractionextracted with ethyl acetate
  4. washthe organic phase was washed with saturated sodium chloride solution
  5. customdried on sodium sulphate
  6. customevaporated down
  7. customThe residue was purified by chromatography (silica gel, petroleum ether/ethyl acetate)

Sources & evidence

ORD record
ord-2e2f01fdf1fb48b7bbc4af1340067b51
Source dataset
uspto-grants-2014_12
Patent number
US08916589B2

Reaction notes

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