Hydrogen Bromide → 5-Bromo-1-chloro-2,3-difluorobenzene

HRID 532192Notes

Reaction equation

HRID 532192 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:6]=[C:7]([F:10])[C:8]=1[F:9])N.N([O-])=O.[Na+].[BrH:15]>O.[Cu]Br>[Br:15][C:4]1[CH:6]=[C:7]([F:10])[C:8]([F:9])=[C:2]([Cl:1])[CH:3]=1

Participants

6

Reactant 3

HCID 260Hydrogen Bromide2×HCID 22343609HCID 22343609, compoundHCID 23668193Sodium Nitrite

Product 1

HCID 509978435-Bromo-1-chloro-2,3-difluorobenzeneYield 68.3%

Reagents, catalysts & solvents 2

HCID 24593copper(I) bromideCatalystHCID 962WaterSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 3-chloro-4,5-difluoroaniline (2.1 g, 12.96 mmol) in hydrobromic acid (40% in H2O, 18.7 mL) was added dropwise a solution of sodium nitrite (0.96 g, 13.6 mol) in 7.5 mL H2O at 0° C. Then the mixture was poured into a solution of copper(I) bromide (3.5 g, 23.7 mmol) in hydrobromic acid (40% in H2O, 15 mL) at 0° C. The cooling bath was then removed and the mixture was heated at 60° C. overnight. After cooling, the mixture was basified with a solution 2N NaOH solution to pH=9 and diluted with CH2Cl2. After separation, the combined organic layers were washed with brine, dried over Na2SO4 and then concentrated to get crude product, which was purified by column with PE/EtOAc (from 100:1 to 20:1) as eluant to afford 2 g product. Yield 68.3%; 1H NMR (400 MHz, CDCl3): δ 7.37-7.35 (m, 1 H), 7.30-7.25 (m, 1 H) ppm.

Workup

  1. customThe cooling bath was then removed
  2. temperatureAfter cooling
  3. additiondiluted with CH2Cl2
  4. customAfter separation
  5. washthe combined organic layers were washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated
  8. customto get crude product, which
  9. customwas purified by column with PE/EtOAc (from 100:1 to 20:1) as eluant

Sources & evidence

ORD record
ord-861e69590808457b96016968ec16719f
Source dataset
uspto-grants-2014_10
Patent number
US08853186B2

Reaction notes

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