Hydrogen Bromide → 5-bromo-2-chloro-4-fluoroanisole

HRID 495017Notes

Reaction equation

HRID 495017 reaction equation
[Cl:1][C:2]1[C:8]([O:9][CH3:10])=[CH:7][C:5](N)=[C:4]([F:11])[CH:3]=1.N([O-])=O.[Na+].C(Cl)Cl.C(OCC)(=O)C.[BrH:25]>O>[Br:25][C:5]1[CH:7]=[C:8]([O:9][CH3:10])[C:2]([Cl:1])=[CH:3][C:4]=1[F:11]

Participants

7

Reactant 5

HCID 260Hydrogen BromideHCID 6344DichloromethaneHCID 8857Ethyl AcetateHCID 1850824-Chloro-2-fluoro-5-methoxyanilineHCID 23668193Sodium Nitrite

Product 1

HCID 102203785-bromo-2-chloro-4-fluoroanisole

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A solution of 4-chloro-2-fluoro-5-methoxyaniline (25.0 g, 0.143 mol) in 10% HBr (250 mL) was cooled to 0° C. and a solution of sodium nitrite (15.0 g, 0.218 mol) in water (20 mL) was slowly added. After addition, methylene chloride (50 mL) and cupric bromide (30.0 g, 0.244 mol) were added slowly. The reaction mixture was then warmed to ambient temperature, stirred for one hour, filtered through a bed of celite, and extracted with methylene chloride (2×100 mL). The combined organic phases were dried and concentrated. Chromatography of the dark oil (5% ethyl acetate in hexanes) gave 1-bromo-4-chloro-2-fluoro-5-methoxybenzene (16.6 g, 0.070 mol): 1H NMR (CDCl3): δ 7.20 (m, 1H), 7.05 (dd, 1H), 4.00 (s, 3H).

Workup

  1. additionwere added slowly
  2. filtrationfiltered through a bed of celite
  3. extractionextracted with methylene chloride (2×100 mL)
  4. customThe combined organic phases were dried
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-91ca4ba98bac44ddbe7e864d2583cca1
Source dataset
uspto-grants-2009_05
Patent number
US07538214B2

Reaction notes

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