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

HRID 1782594Notes

Reaction equation

HRID 1782594 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=O)C.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 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 mixture was stirred 1 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 to 70° C. for 18 hours. The solution was diluted with water (200 mL) and extracted with ethyl ether. The combined organic phases were dried (sodium sulfate) and concentrated. The residual oil was purified by 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 7.3 (m, 1H), 7.10 (dd, 1H), 6.15 (dt, 1H), 4.35 (m, 2H).

Workup

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

Sources & evidence

ORD record
ord-c5668ed9c68646b79a8599eb7a65ab66
Source dataset
uspto-grants-2009_03
Patent number
US07498468B2

Reaction notes

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