Hydrogen Bromide → Methyl 2-bromo-4-fluoro-5-methylbenzoate

HRID 532232Notes

Reaction equation

HRID 532232 reaction equation
N[C:2]1[CH:11]=[C:10]([F:12])[C:9]([CH3:13])=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].N([O-])=O.[Na+].C(OCC)(=O)C.[BrH:24]>[Cu]Br>[Br:24][C:2]1[CH:11]=[C:10]([F:12])[C:9]([CH3:13])=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5]

Participants

6

Reactant 4

HCID 260Hydrogen BromideHCID 8857Ethyl AcetateHCID 23668193Sodium NitriteHCID 58115582Methyl 2-amino-4-fluoro-5-methylbenzoate

Product 1

HCID 86685092Methyl 2-bromo-4-fluoro-5-methylbenzoateYield 74%

Reagents, catalysts & solvents 1

HCID 24593copper(I) bromideCatalyst

Procedure

To the suspension of methyl 2-amino-4-fluoro-5-methylbenzoate (2.2 g, 12 mmol) in 48% hydrobromic acid (80 mL) was added an aqueous solution (32 mL) of sodium nitrite (828 mg, 12 mmol) at 0° C., and the resulting solution was stirred for 30 min. Copper (I) bromide (1.72 g, 12 mmol) was added to the solution at 0° C. and the resulting reaction mixture was stirred at r.t for 1 h. After addition of ethyl acetate (200 mL), the reaction mixture was washed with water (200 mL×2), dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel eluted with PE-EA (10:1) to give methyl 2-bromo-4-fluoro-5-methylbenzoate (2.2 g, yield 74%) as colorless oil. 1H NMR (500 MHz, CDCl3) δ 7.655 (d, J=8.0 Hz, 1H), 7.257 (d, J=8.5 Hz, 1H), 3.837 (s, 3H), 2.177 (s, 3H) ppm.

Workup

  1. customthe resulting reaction mixture
  2. stirringwas stirred at r.t for 1 h
  3. washthe reaction mixture was washed with water (200 mL×2)
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by column chromatography on silica gel
  8. washeluted with PE-EA (10:1)

Sources & evidence

ORD record
ord-94ec4a375eb4499db4740d6c9178b735
Source dataset
uspto-grants-2014_10
Patent number
US08853186B2

Reaction notes

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