Hydrogen Bromide → 4-Bromo-2-(trifluoromethyl)benzonitrile

HRID 872570Notes

Reaction equation

HRID 872570 reaction equation
N[C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([C:10]([F:13])([F:12])[F:11])[CH:3]=1.N([O-])=O.[Na+].[BrH:18]>O.[Cu]Br>[Br:18][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([C:10]([F:13])([F:12])[F:11])[CH:3]=1

Participants

6

Reactant 3

HCID 260Hydrogen Bromide2×HCID 5221704-Amino-2-(trifluoromethyl)benzonitrileHCID 23668193Sodium Nitrite

Product 1

HCID 223378254-Bromo-2-(trifluoromethyl)benzonitrile

Reagents, catalysts & solvents 2

HCID 24593copper(I) bromideCatalystHCID 962WaterSolvent

Procedure

To the cooled and vigorously stirred suspension of 4-amino-2-(trifluoromethyl)benzonitrile (5.00 g, 26.8 mmol) in 25 ml of concentrated hydrogen bromide a solution of sodium nitrite (1.85 g, 26.8 mmol) in 10 ml of water was added dropwise while keeping the temperature below 5° C. during the addition. This mixture was then poured into a solution of copper(I)bromide (3.85 g, 26.8 mmol) in 30 ml of concentrated hydrogen bromide and stirred at RT for two hours. The reaction mixture was then poured into an ice-water (300 ml) mixture and extracted four times with ethyl acetate. The combined extracts were washed with saturated sodium bicarbonate and water, dried and evaporated to dryness. Combiflash purification using heptane/ethyl acetate as eluent system afforded 5.1 g of the title product. 1H-NMR (400 MHz; d6-DMSO): δ 8.13 (d, 1H), 8.18 (d, 1H), 8.27 (s, 1H)

Workup

  1. temperatureTo the cooled
  2. additionwas added dropwise
  3. customthe temperature below 5° C.
  4. additionduring the addition
  5. extractionextracted four times with ethyl acetate
  6. washThe combined extracts were washed with saturated sodium bicarbonate and water
  7. customdried
  8. customevaporated to dryness
  9. customCombiflash purification

Sources & evidence

ORD record
ord-270088fdaa664599ac3b1d0178d3e4e1
Source dataset
uspto-grants-2015_03
Patent number
US08975254B2

Reaction notes

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