Sodium Hydroxide → 2-Bromo-1-chloro-3-fluorobenzene

HRID 382503Notes

Reaction equation

HRID 382503 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[CH:3]=1.C([Li])CCC.[Br:14]Br.S([O-])([O-])=O.[Na+].[Na+].[OH-].[Na+]>O1CCCC1.O>[Br:14][C:3]1[C:4]([F:8])=[CH:5][CH:6]=[CH:7][C:2]=1[Cl:1]

Participants

8

Reactant 5

HCID 14798Sodium HydroxideHCID 24408BromineHCID 24437Sodium SulfiteHCID 2230871-Chloro-3-fluorobenzeneHCID 178418339Butyllithium

Product 1

HCID 219386602-Bromo-1-chloro-3-fluorobenzene

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 261.1 g (2.0 mol) of 1-chloro-3-fluorobenzene in 2000 ml of dry tetrahydrofuran under nitrogen is cooled to −78°. To the solution is added 960 ml (2.4 mol) of 2.5 M n-butyllithium in hexanes over a period of 40 minutes. After stirring for 2.5 hours, a slurry of 155 ml of bromine cooled to −78° is added over 30 minutes and the mixture is stirred for 40 minutes before warming to −10°. The reaction is quenched with an aqueous solution of 151.3 g (1.2 mol) of sodium sulfite and 16.0 g (0.4 mol) of sodium hydroxide in 500 ml of water. The organic layer is separated, the solvents are removed at ambient pressure, and the product is distilled at 92-96° (20 mm Hg) to obtain 2-bromo-3-fluoro-chlorobenzene as a colorless oil.

Workup

  1. additionis added over 30 minutes
  2. stirringthe mixture is stirred for 40 minutes
  3. temperaturebefore warming to −10°
  4. customThe organic layer is separated
  5. customthe solvents are removed at ambient pressure
  6. distillationthe product is distilled at 92-96° (20 mm Hg)

Sources & evidence

ORD record
ord-0af24e102ba04d479bb8a2b0ac3768bd
Source dataset
uspto-grants-2001_10
Patent number
US06310099B1

Reaction notes

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