3-Bromo-5-(trifluoromethyl)benzoic acid → 3-Cyano-5-(trifluoromethyl)benzoic acid

HRID 1055659Notes

Reaction equation

HRID 1055659 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:10]=1)[C:5]([OH:7])=[O:6].[CH3:15][N:16](C=O)C.O>[C-]#N.[Zn+2].[C-]#N>[C:15]([C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:10]=1)[C:5]([OH:7])=[O:6])#[N:16]

Participants

4

Reactant 2

HCID 110867883-Bromo-5-(trifluoromethyl)benzoic acid2×HCID 21962138N,N-Dimethylformamide--water (1/1)

Product 1

HCID 589022873-Cyano-5-(trifluoromethyl)benzoic acid

Reagents, catalysts & solvents 1

HCID 11186Zinc cyanide (Zn(CN)2)Catalyst

Conditions

Temperature
120 °C

Procedure

A mixture of 2.0 g (7.43 mmol) of 3-bromo-5-(trifluoromethyl)benzoic acid [US 2006/0069261-A1, compound 1.2], 995 mg (8.48 mmol) of zinc cyanide and 859 mg (0.743 mmol) of tetrakis-(triphenylphosphine)palladium(0) in 75 ml of DMF/water (99:1) was initially degassed and then, under an atmosphere of argon, heated at 120° C. for 3 h. After cooling to RT, the mixture was diluted with about 300 ml of water and extracted three times with in each case about 150 ml of ethyl acetate. The combined organic extracts were washed with saturated sodium chloride solution, dried over anhydrous magnesium sulphate, filtered and then concentrated to dryness on a rotary evaporator. The product was isolated by preparative HPLC (Method 9). Evaporation of the product fractions and drying of the residue under high vacuum gave 421 mg (26% of theory) of the title compound.

Workup

  1. customwas initially degassed
  2. temperatureAfter cooling to RT
  3. additionthe mixture was diluted with about 300 ml of water
  4. extractionextracted three times with in each case about 150 ml of ethyl acetate
  5. washThe combined organic extracts were washed with saturated sodium chloride solution
  6. dry with materialdried over anhydrous magnesium sulphate
  7. filtrationfiltered
  8. concentrationconcentrated to dryness on a rotary evaporator
  9. customThe product was isolated by preparative HPLC (Method 9)
  10. customEvaporation of the product fractions
  11. customdrying of the residue under high vacuum

Sources & evidence

ORD record
ord-567a3bd77f1f4842ac637db4d702ccea
Source dataset
uspto-grants-2016_07
Patent number
US09394309B2

Reaction notes

Loading…