Tetrahydrofuran → 1-Bromo-3-difluoromethyl-5-(4-methoxy-benzyloxy)-benzene

HRID 20263Notes

Reaction equation

HRID 20263 reaction equation
C[C:2]([CH3:5])([O-])[CH3:3].[K+].[CH2:7]1[CH2:11][O:10][CH2:9][CH2:8]1.F[C:13]1[CH:14]=[C:15]([Br:22])[CH:16]=[C:17]([CH:19]([F:21])[F:20])[CH:18]=1.[C:23]([O-])(O)=[O:24].[Na+]>C1(C)C=CC=CC=1.O>[Br:22][C:15]1[CH:14]=[C:13]([O:24][CH2:23][C:3]2[CH:8]=[CH:7][C:11]([O:10][CH3:9])=[CH:5][CH:2]=2)[CH:18]=[C:17]([CH:19]([F:21])[F:20])[CH:16]=1

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 516892Sodium BicarbonateHCID 222402791-Bromo-3-(difluoromethyl)-5-fluorobenzeneHCID 23665647Potassium tert-butoxide

Product 1

HCID 669380551-Bromo-3-difluoromethyl-5-(4-methoxy-benzyloxy)-benzene

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
65 °C

Procedure

steps 3-5—p-Methoxybenzyl alcohol (36.8 g, 266.7 mmol) was added slowly to a mixture of potassium t-butoxide (28.7 g, 255.5 mol) and THF (250 mL). After stirring for about 15 min, 30 (50.0 g, 222.2 mmol) was added and the reaction mixture heated to about 65° C. After stirring at 65° C. for 2 h, the reaction is analyzed by HPLC. After cooling to RT, a mixture of saturated NaHCO3 solution (150 mL) and water (150 mL) was added. Toluene (300 mL) was added, the organic phase separated and washed with a mixture of saturated NaHCO3 solution (75 mL) and water (75 mL). Polish filtration and concentration in vacuo provided 83.9 g of crude 32 as an oil which is used without further purification.

Workup

  1. stirringAfter stirring at 65° C. for 2 h
  2. temperatureAfter cooling to RT
  3. additionwas added
  4. customthe organic phase separated
  5. washwashed with a mixture of saturated NaHCO3 solution (75 mL) and water (75 mL)
  6. filtrationPolish filtration and concentration in vacuo

Sources & evidence

ORD record
ord-c43049994fb74c3287a1354e12a3fa65
Source dataset
uspto-grants-2010_06
Patent number
US07745634B2

Reaction notes

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