Sodium hydride → 1-Bromo-4-chloro-3-(2,2-difluoroethoxy)-2-fluorobenzene

HRID 1363929Notes

Reaction equation

HRID 1363929 reaction equation
[Br:1][C:2]1[C:3]([F:10])=[C:4]([OH:9])[C:5]([Cl:8])=[CH:6][CH:7]=1.[H-].[Na+].[F:13][CH:14]([F:21])[CH2:15]OS(C)(=O)=O>CN(C)C=O.O>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[C:4]([O:9][CH2:15][CH:14]([F:21])[F:13])[C:3]=1[F:10]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 567764922,2-Difluoroethyl methanesulfonateHCID 666010023-Bromo-6-chloro-2-fluorophenol

Product 1

HCID 866138401-Bromo-4-chloro-3-(2,2-difluoroethoxy)-2-fluorobenzeneYield 45.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent3×

Conditions

Temperature
70 °C

Procedure

A solution of 3-bromo-6-chloro-2-fluorophenol (15.4 g, 0.068 mol) in dimethylformamide (DMF; 25 mL) was slowly added to a suspension of sodium hydride (60% dispersion in mineral oil) (4.0 g, 0.10 mol) in DMF (100 mL) and the reaction mixture was stirred one hour. A solution of methanesulfonic acid 2,2-difluoroethyl ester (17.5 g, 0.109 mol) in DMF (10 mL) was slowly added. The resulting solution was heated at 70° C. for eighteen hours. The cooled solution was diluted with water (200 mL) and extracted with ethyl ether. The combined organic phases were dried and concentrated. The residual oil was purified by column chromatography (in hexanes) to give 1-bromo-4-chloro-3-(2,2-difluoroethoxy)-2-fluorobenzene (9.0 g, 0.031 mol): 1H NMR (CDCl3): δ 7.26 (m, 1H), 7.09 (m, 1H), 6.12 (tt, 1H), 4.30 (td, 2H).

Workup

  1. extractionextracted with ethyl ether
  2. customThe combined organic phases were dried
  3. concentrationconcentrated
  4. customThe residual oil was purified by column chromatography (in hexanes)

Sources & evidence

ORD record
ord-9d33cd6dcbe34c7f95a0145af00e287e
Source dataset
uspto-grants-2011_02
Patent number
US07888287B2

Reaction notes

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