Sodium hydride → 3-Bromo-4-fluorobenzyl 2,2-dimethyl-2-(4-ethoxyphenyl)ethyl ether

HRID 638635

Reaction equation

HRID 638635 reaction equation
[H-].[Na+].[CH3:3][C:4]([CH3:16])([C:7]1[CH:12]=[CH:11][C:10]([O:13][CH2:14][CH3:15])=[CH:9][CH:8]=1)[CH2:5][OH:6].[Br:17][C:18]1[CH:19]=[C:20]([CH:23]=[CH:24][C:25]=1[F:26])[CH2:21]Br>CN(C)C=O>[CH3:3][C:4]([CH3:16])([C:7]1[CH:8]=[CH:9][C:10]([O:13][CH2:14][CH3:15])=[CH:11][CH:12]=1)[CH2:5][O:6][CH2:21][C:20]1[CH:23]=[CH:24][C:25]([F:26])=[C:18]([Br:17])[CH:19]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 1585252-(4-Ethoxyphenyl)-2-methylpropanolHCID 129227103-Bromo-4-fluorobenzyl Bromide

Product 1

HCID 134881903-Bromo-4-fluorobenzyl 2,2-dimethyl-2-(4-ethoxyphenyl)ethyl etherYield 41.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

657 Milligrams of sodium hydride (as 60% oil suspension) was added to 10 ml of dimethylformamide, and 3.19 g of 2,2-dimethyl-2-(4-ethoxyphenyl)ethanol was added dropwise. Thereafter, the reaction solution was warmed to 50° C. and stirred for 10 minutes, and 4.0 g of 3-bromo-4-fluorobenzyl bromide was added dropwise thereto at 20° C. After completion of the dropwise addition, stirring was continued at 50° C. for further 5 hours, and the reaction solution was then poured into a 5% hydrochloric acid/ice water mixture and extracted with ethyl acetate. The ethyl acetate layer was washed with an aqueous sodium chloride liquor and dried over anhydrous magnesium sulfate. After removing the solvent by evaporation, the residual oil was purified by column chromatography on a column packed with 60 g of silica gel to obtain 2.37 g of 3-bromo-4-fluorobenzyl 2,2-dimethyl-2-(4-ethoxyphenyl)ethyl ether. 1H-NMR spectrum (CDCl3, TMS). δ 7.4-6.5 (7H, m), δ 4.30 (2H, s), δ 3.99 (2H, q), δ 3.34 (2H, s), δ 1.36 (3H, t), δ 1.30 (6H, s).

Workup

  1. additionwas added dropwise
  2. customat 20° C
  3. additionAfter completion of the dropwise addition
  4. stirringstirring
  5. waitwas continued at 50° C. for further 5 hours
  6. extractionextracted with ethyl acetate
  7. washThe ethyl acetate layer was washed with an aqueous sodium chloride liquor
  8. dry with materialdried over anhydrous magnesium sulfate
  9. customAfter removing the solvent
  10. customby evaporation
  11. customthe residual oil was purified by column chromatography on a column

Sources & evidence

ORD record
ord-df932647de5b4769ac1dd2e1faf8da60
Source dataset
uspto-grants-1985_12
Patent number
US04562213

Linked notes

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