Hydrochloric Acid → 3-Bromo-5-fluorophenol

HRID 20434Notes

Reaction equation

HRID 20434 reaction equation
[Cl-].[Al+3].[Cl-].[Cl-].C([O:12][C:13]1[CH:18]=[C:17]([F:19])[CH:16]=[C:15]([Br:20])[CH:14]=1)C1C=CC=CC=1.CN(C)C1C=CC=CC=1.Cl>ClCCl>[Br:20][C:15]1[CH:14]=[C:13]([OH:12])[CH:18]=[C:17]([F:19])[CH:16]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 949N,N-DimethylanilineHCID 6451240Aluminum(III) ChlorideHCID 112545161-(Benzyloxy)-3-bromo-5-fluorobenzene

Product 1

HCID 219046363-Bromo-5-fluorophenolYield 66.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Add aluminum chloride (13.51 g, 101.38 mmol) to 1-benzyloxy-3-bromo-5-fluoro-benzene (9.50 g, 33.79 mmol, prepared according to WO 03/101956) and dimethylaniline (40.96 g, 337.92 mmol) in dichloromethane (84 mL) at −0° C. under nitrogen and stir 10 minutes. Remove ice-bath and stir 2 hours. Add 60 mL 2N hydrochloric acid dropwise. Separate layers and wash the organic layer with 2N hydrochloric acid (4×50 mL). Extract the organic layer with 3N potassium hydroxide (4×50 mL). Acidify with 5N hydrochloric acid and extract with dichloromethane (3×50 mL). Dry the dichloromethane layer (sodium sulfate) and concentrate to give 4.3 g (66.6%) of the desired compound as an oil.

Workup

  1. stirringRemove ice-bath and stir 2 hours
  2. washSeparate layers and wash the organic layer with 2N hydrochloric acid (4×50 mL)
  3. extractionExtract the organic layer with 3N potassium hydroxide (4×50 mL)
  4. extractionAcidify with 5N hydrochloric acid and extract with dichloromethane (3×50 mL)
  5. dry with materialDry the dichloromethane layer (sodium sulfate)
  6. concentrationconcentrate

Sources & evidence

ORD record
ord-28b48af1d26e4a6692ef54e482230323
Source dataset
uspto-grants-2010_06
Patent number
US07745438B2

Reaction notes

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