Water → Methyl 4-cyano-2-fluorobenzoate
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.O.C(OCC)(=O)C.[CH3:20][N:21](C=O)C>[C-]#N.[Zn+2].[C-]#N>[C:20]([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:21]Participants
Conditions
- Temperature
- 100 °C
Procedure
To a solution of methyl 4-bromo-2-fluorobenzoate (9.1 mmol) in DMF (50 mL) was added zinc cyanide (641 mg, 5.5 mmol) followed by tetrakis(triphenyphosphine)palladium(0) (1.05 g, 0.91 mmol). The mixture was heated to 100° C. and stirred for 3 h. At that point, additional tetrakis(triphenyphosphine)-palladium(0) (500 mg, 0.43 mmol) was added. The mixture was stirred a further 30 min and was then cooled to room temperature. Water and ethyl acetate were added, and insoluble solids were removed by filtration through celite. The layers were then separated. The aqueous phase was extracted with ethyl acetate. The organic extracts were combined, washed with 10% aqueous lithium chloride, dried over magnesium sulfate, filtered and concentrated. The residue was purified by column chromatography (10% ethyl acetate in hexanes) to provide methyl 4-cyano-2-fluorobenzoate (1.36 g, 7.6 mmol, 84% yield).
Workup
- stirringThe mixture was stirred a further 30 min
- temperaturewas then cooled to room temperature
- custominsoluble solids were removed by filtration through celite
- customThe layers were then separated
- extractionThe aqueous phase was extracted with ethyl acetate
- washwashed with 10% aqueous lithium chloride
- dry with materialdried over magnesium sulfate
- filtrationfiltered
- concentrationconcentrated
- customThe residue was purified by column chromatography (10% ethyl acetate in hexanes)
Sources & evidence
- ORD record
- ord-88d57607c9714ce489e3d884718b5e7a
- Source dataset
- uspto-grants-2011_09
- Patent number
- US08012956B2
Reaction notes
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