Phenethyl bromide → 3-(2-Chloro-4-phenethyloxy-phenyl)-1,1,1-trifluoro-2-(2-methyl-pyridin-4-yl)-butan-2-ol

HRID 333792Notes

Reaction equation

HRID 333792 reaction equation
[H-].[Na+].[Cl:3][C:4]1[CH:5]=[C:6]([OH:25])[CH:7]=[CH:8][C:9]=1[CH:10]([CH3:24])[C:11]([OH:23])([C:16]1[CH:21]=[CH:20][N:19]=[C:18]([CH3:22])[CH:17]=1)[C:12]([F:15])([F:14])[F:13].Br[CH2:27][CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1>CN(C=O)C>[Cl:3][C:4]1[CH:5]=[C:6]([O:25][CH2:27][CH2:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH:7]=[CH:8][C:9]=1[CH:10]([CH3:24])[C:11]([C:16]1[CH:21]=[CH:20][N:19]=[C:18]([CH3:22])[CH:17]=1)([OH:23])[C:12]([F:15])([F:13])[F:14]

Participants

5

Reactant 3

HCID 7666Phenethyl bromideHCID 24758Sodium hydrideHCID 252541463-Chloro-4-[3,3,3-trifluoro-2-hydroxy-1-methyl-2-(2-methyl-pyridin-4-yl)-propyl]-phenol

Product 1

HCID 574212483-(2-Chloro-4-phenethyloxy-phenyl)-1,1,1-trifluoro-2-(2-methyl-pyridin-4-yl)-butan-2-ol

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

Sodium hydride (60% in mineral oil, 20.4 mg) was added to abs. DMF (2 mL). To this mixture was added a solution of 3-chloro-4-[3,3,3-trifluoro-2-hydroxy-1-methyl-2-(2-methyl-pyridin-4-yl)-propyl]-phenol (Example 73, 80 mg) in DMF (2 mL) over 15 minutes. The mixture was then allowed to stir for 30 min at RT. The mixture was cooled to 0° C. and a solution of 2-bromoethylbenzene ((0.033 mL) in DMF (1 mL) was added within 10 minutes. The mixture was then heated to 50° C. over night. The reaction mixture was poured into ice/water and extracted with ethyl acetate. The organic extracts were washed with brine, dried over Na2SO4 and evaporated. The residue was purified by flash chromatography (silica gel, gradient of ethyl acetate in heptane) to give the title compound as a colorless oil (12 mg). MS (m/e)=450.2 (MH+).

Workup

  1. temperatureThe mixture was cooled to 0° C.
  2. temperatureThe mixture was then heated to 50° C. over night
  3. extractionextracted with ethyl acetate
  4. washThe organic extracts were washed with brine
  5. dry with materialdried over Na2SO4
  6. customevaporated
  7. customThe residue was purified by flash chromatography (silica gel, gradient of ethyl acetate in heptane)

Sources & evidence

ORD record
ord-9db2cbf1f7ca4749b566e8f3cd533094
Source dataset
uspto-grants-2014_11
Patent number
US08883786B2

Reaction notes

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