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

HRID 1782592Notes

Reaction equation

HRID 1782592 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.[Br-:19]>Br.O.C(OCC)(=O)C>[Br:19][C:5]1[CH:7]=[C:8]([O:9][CH3:10])[C:2]([Cl:1])=[CH:3][C:4]=1[F:11]

Participants

8

Reactant 4

HCID 259Bromide ionHCID 6344DichloromethaneHCID 1850824-Chloro-2-fluoro-5-methoxyanilineHCID 23668193Sodium Nitrite

Product 1

HCID 102203785-bromo-2-chloro-4-fluoroanisoleYield 49%

Reagents, catalysts & solvents 3

HCID 260Hydrogen BromideSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

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. Methylene chloride (50 mL) and curpric bromide (30.0 g, 0.244 mol) were added slowly and then the mixture was warmed to ambient temperature and stirred for 1 hour. The reaction mixture was filtered through a bed of celite and extracted with methylene chloride (2×100 mL) and the combined organic phases were dried (sodium sulfate) 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. filtrationThe reaction mixture was filtered through a bed of celite and
  2. extractionextracted with methylene chloride (2×100 mL)
  3. dry with materialthe combined organic phases were dried (sodium sulfate)
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-9e31a094b5ad4c52a5d3d502c4b2d626
Source dataset
uspto-grants-2009_03
Patent number
US07498468B2

Reaction notes

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