Ethyl Acetate → 1-Bromo-2-(2-(ethoxymethoxy)-1,3-difluoropropan-2-yl)-4-methylbenzene

HRID 1750825Notes

Reaction equation

HRID 1750825 reaction equation
[H-].[Na+].[Br:3][C:4]1[CH:9]=[CH:8][C:7]([CH3:10])=[CH:6][C:5]=1[C:11]([OH:16])([CH2:14][F:15])[CH2:12][F:13].[CH2:17](Cl)[O:18][CH2:19][CH2:20]OC.CC(=O)OCC>C1COCC1.O>[Br:3][C:4]1[CH:9]=[CH:8][C:7]([CH3:10])=[CH:6][C:5]=1[C:11]([O:16][CH2:17][O:18][CH2:19][CH3:20])([CH2:12][F:13])[CH2:14][F:15]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 775901-(Chloromethoxy)-2-methoxyethaneHCID 866850732-(2-Bromo-5-methylphenyl)-1,3-difluoropropan-2-ol

Product 1

HCID 866850741-Bromo-2-(2-(ethoxymethoxy)-1,3-difluoropropan-2-yl)-4-methylbenzeneYield 73.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

NaH (362 mg, 9.05 mmol) was added to a solution of 2-(2-bromo-5-methylphenyl)-1,3-difluoropropan-2-ol (2.0 g, 7.54 mmol) in THF (10 mL) slowly at 0° C. MEMCl (1.41 g, 11.32 mmol) was added dropwise. The mixture was stirred at rt overnight. The mixture was diluted with H2O and extracted with EA (50 mL×2). The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by column chromatography over silica gel eluted with PE:EA (10:1 to 6:1) to give the product (1.8 g, yield 68%) as colorless oil.

Workup

  1. extractionextracted with EA (50 mL×2)
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by column chromatography over silica gel
  7. washeluted with PE

Sources & evidence

ORD record
ord-ef8b92b0f98e4d2d87717b5e740d478f
Source dataset
uspto-grants-2015_10
Patent number
US09156860B2

Reaction notes

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