Dimethylformamide → Methyl 4-cyano-2-fluorobenzoate

HRID 2374682Notes

Reaction equation

HRID 2374682 reaction equation
Br[C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([F:12])[CH:3]=1.[CH3:13][N:14](C)C=O>[C-]#N.[Zn+2].[C-]#N.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Pd]>[C:13]([C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([F:12])[CH:3]=1)#[N:14]

Participants

5

Reactant 2

HCID 6228DimethylformamideHCID 113453114-Bromo-2-fluoro-benzoic acid methyl ester

Product 1

HCID 15278726Methyl 4-cyano-2-fluorobenzoateYield 80%

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 11979704Tetrakis(triphenylphosphine)palladiumCatalyst

Conditions

Temperature
80 °C

Procedure

A solution of methyl 4-bromo-2-fluorobenzoate (10.0 g, 43 mmol), zinc cyanide (10.0 g, 86 mmol) and palladium tetrakis(triphenylphosphine) (2.5 g, 0.64 mmol) in anhydrous N,N-dimethylformamide (100 mL) was purged with nitrogen and the mixture stirred at 80° C. overnight. After cooling, the mixture was partitioned between ethyl acetate and brine and the organic phase washed with water and concentrated. The solid was purified on silica gel using 1:5 ethyl acetate/hexane to afford the title compound (6.1 g, 80%). MS (DCI): m/z 180 (M+H)+.

Workup

  1. temperatureAfter cooling
  2. customthe mixture was partitioned between ethyl acetate and brine
  3. washthe organic phase washed with water
  4. concentrationconcentrated
  5. customThe solid was purified on silica gel using 1:5 ethyl acetate/hexane

Sources & evidence

ORD record
ord-0ffb61fcded345929de38e2b3f75dd7e
Source dataset
uspto-grants-2008_12
Patent number
US07462724B2

Reaction notes

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