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

HRID 532205Notes

Reaction equation

HRID 532205 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-a222f46096a84d0eae3af2f354273d89
Source dataset
uspto-grants-2014_10
Patent number
US08853186B2

Reaction notes

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