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

HRID 1593962Notes

Reaction equation

HRID 1593962 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-ef1f674086cf4070925e336c8ea8611e
Source dataset
uspto-grants-2007_11
Patent number
US07300907B2

Reaction notes

Loading…