Dimethylformamide → 4-Cyano-3-fluorobenzoic acid

HRID 1524869Notes

Reaction equation

HRID 1524869 reaction equation
Br[C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][C:3]=1[F:11].[CH3:12][N:13](C=O)C>[C-]#N.[C-]#N.[Zn+2].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:12]([C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][C:3]=1[F:11])#[N:13]

Participants

5

Reactant 2

HCID 6228DimethylformamideHCID 27733414-Bromo-3-fluorobenzoic acid

Product 1

HCID 27784684-Cyano-3-fluorobenzoic acid

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
90 °C

Procedure

4-Bromo-3-fluorobenzoic acid (7.5 g, 0.034 mol), Zn(CN)2 (4.0 g, 0.034 mol) and Pd(PPh3)4 (3.95 g, 0.0034 mol) were added together with 60 mL of DMF (degassed). The mixture was heated at 90° C. under N2 for 3 h. It was cooled to room temperature and filtered to remove insoluble inorganic salts (discarded). The filtrate was diluted with water and extracted with EtOAc. The EtOAc mixture was washed with water, brine, dried over MgSO4, and concentrated to yield 4.5 g of the desired product with 90% purity. This material was taken into the next step without further purification. 1H-NMR (500 MHz, d4-MeOH) δ 7.82 (m, 1H), 7.90 (m, 3H), 7.56 (d, J=10.0 Hz, 1H), 7.68 (s, 1H), 7.96 (d, J=8.4 Hz, 1H).

Workup

  1. temperatureIt was cooled to room temperature
  2. filtrationfiltered
  3. customto remove insoluble inorganic salts (discarded)
  4. additionThe filtrate was diluted with water
  5. extractionextracted with EtOAc
  6. washThe EtOAc mixture was washed with water, brine
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-847f57cd1a61409ea33575bfb751f66c
Source dataset
uspto-grants-2015_07
Patent number
US09079860B2

Reaction notes

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