Sodium hydride → 2-(4-Ethoxyphenyl)-3,3,3-trifluoropropyl 3-(4-fluorophenoxy)benzyl ether

HRID 1904973Notes

Reaction equation

HRID 1904973 reaction equation
[H-].[Na+].[CH2:3]([O:5][C:6]1[CH:11]=[CH:10][C:9]([CH:12]([C:15]([F:18])([F:17])[F:16])[CH2:13][OH:14])=[CH:8][CH:7]=1)[CH3:4].[F:19][C:20]1[CH:34]=[CH:33][C:23]([O:24][C:25]2[CH:26]=[C:27]([CH:30]=[CH:31][CH:32]=2)[CH2:28]Br)=[CH:22][CH:21]=1>CN(C=O)C>[F:19][C:20]1[CH:34]=[CH:33][C:23]([O:24][C:25]2[CH:26]=[C:27]([CH:30]=[CH:31][CH:32]=2)[CH2:28][O:14][CH2:13][CH:12]([C:9]2[CH:8]=[CH:7][C:6]([O:5][CH2:3][CH3:4])=[CH:11][CH:10]=2)[C:15]([F:16])([F:17])[F:18])=[CH:22][CH:21]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 27374563-(4-Fluorophenoxy)benzyl BromideHCID 10681171(RS)-1,1,1-trifluoro-2-(4-ethoxyphenyl)propan-3-ol

Product 1

HCID 145808142-(4-Ethoxyphenyl)-3,3,3-trifluoropropyl 3-(4-fluorophenoxy)benzyl etherYield 77.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

Under a nitrogen atmosphere, 171 mg of sodium hydride (60% oil dispersion) was added to 15 ml of dry DMF. A solution of 1.0 g of 2-(4-ethoxyphenyl)-3,3,3-trifluoropropanol and 1.08 g of 3-(4-fluorophenoxy)-benzyl bromide in 20 ml of dry DMF was then added with ice-cooling, and the reaction solution was stirred with ice-cooling for 1 hour and at room temperature for 12 hours. Thereafter, the reaction mixture was poured into dilute HCl-ice water and extracted twice with diethyl ether. The ether layers were combined, washed with saturated sodium chloride solution and dried over anhydrous magnesium sulfate. The solvent was removed under a reduced pressure, and the residue was subjected to column chromatography on silica gel [eluted with n-hexane/ethyl acetate (25:1) mixture] to obtain 1.30 g of the desired compound.

Workup

  1. temperaturecooling
  2. extractionextracted twice with diethyl ether
  3. washwashed with saturated sodium chloride solution
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customThe solvent was removed under a reduced pressure

Sources & evidence

ORD record
ord-3db15275476d4c50894ba5f8873e0988
Source dataset
uspto-grants-1989_06
Patent number
US04840971

Reaction notes

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