3-Hydroxybenzyl alcohol → (3-(4-(Trifluoromethyl)phenoxy)phenyl)methanol

HRID 539852Notes

Reaction equation

HRID 539852 reaction equation
Cl[C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][CH:3]=1.[OH:12][C:13]1[CH:14]=[C:15]([CH:18]=[CH:19][CH:20]=1)[CH2:16][OH:17].C(=O)([O-])[O-].[K+].[K+].CN1CCN(C)C1=O>[Cu]Cl.N1C2C(=CC=CC=2O)C=CC=1.O>[F:9][C:8]([F:11])([F:10])[C:5]1[CH:6]=[CH:7][C:2]([O:12][C:13]2[CH:14]=[C:15]([CH:18]=[CH:19][CH:20]=2)[CH2:16][OH:17])=[CH:3][CH:4]=1

Participants

8

Reactant 4

HCID 1023-Hydroxybenzyl alcoholHCID 66611,3-Dimethyl-2-imidazolidinoneHCID 73941-Chloro-4-(trifluoromethyl)benzeneHCID 11430Potassium Carbonate

Product 1

HCID 23136407(3-(4-(Trifluoromethyl)phenoxy)phenyl)methanolYield 42.2%

Reagents, catalysts & solvents 3

HCID 19238-HydroxyquinolineCatalystHCID 62652Cuprous chlorideCatalystHCID 962WaterSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of 4-chlorobenzotrifluoride (27.1 g, 1.5 equiv), 3-hydroxybenzyl alcohol (12.4 g, 1 equiv), copper (I) chloride (0.2 g, 0.02 equiv), potassium carbonate (8.3 g, 0.6 equiv), 8-quinolinol (0.29 g, 0.02 equiv) and 1,3-dimethyl-2-imidazolidinone (50 mL) was stirred at 150° C. under argon for 3 days. After cooling, the residue was poured into water and extracted with ethyl acetate. Drying and evaporation, followed by chromatography (silica, dichloromethane) gave the title compound as a pale liquid (11.3 g). 1H-NMR (CDCl3) δ 1.88 (1H, t), 4.69 (2H, d), 6.97 (1H, m), 7.04 (3H, m), 7.17 (1H, m), 7.36 (1H, m), 7.57 (2H, m); MS (APCI−) found (M−1)=267; C14H11F3O2 requires 268.

Workup

  1. temperatureAfter cooling
  2. extractionextracted with ethyl acetate
  3. customDrying
  4. customevaporation

Sources & evidence

ORD record
ord-ba0cae49303140f3b1f38d8480341205
Source dataset
uspto-grants-2014_10
Patent number
US08871775B2

Reaction notes

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