Dimethylformamide → 2-Amino-3-chloro-5-fluorobenzonitrile
Reaction equation
Br[C:2]1[CH:8]=[C:7]([F:9])[CH:6]=[C:5]([Cl:10])[C:3]=1[NH2:4].[CH3:11][N:12](C=O)C>[Cl-].[Na+].O.[C-]#N.[Zn+2].[C-]#N.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>[NH2:4][C:3]1[C:5]([Cl:10])=[CH:6][C:7]([F:9])=[CH:8][C:2]=1[C:11]#[N:12]Participants
6
Reactant 2
Product 1
Reagents, catalysts & solvents 3
Conditions
- Temperature
- 80 °C
Procedure
A mixture of 2-bromo-6-chloro-4-fluoroaniline (6.0 g, 26.7 mmol), zinc cyanide (11.42 g, 97.6 mmol) and Pd(PPh3)4 (2.16 g, 1.92 mmol) in anhydrous DMF (84 mL) was heated at 80° C., under an atmosphere of argon for 24 hours. The reaction mixture was cooled and diluted with brine. This mixture was extracted with ethyl acetate (×3) and the combined organic layers were washed with water (×2), dried, filtered and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (0-20% ethyl acetate in cyclohexane) to afford the title compound as a pale yellow solid (3.29 g, 72% yield). 1H NMR (300 MHz, CDCl3): δ 7.27 (dd, J=7.9, 2.9 Hz, 1H), 7.08 (dd, J=7.6, 2.9 Hz, 1H), 4.67 (br s, 2H).
Workup
- temperatureThe reaction mixture was cooled
- extractionThis mixture was extracted with ethyl acetate (×3)
- washthe combined organic layers were washed with water (×2)
- customdried
- filtrationfiltered
- concentrationconcentrated under reduced pressure
- customThe residue was purified by silica gel flash chromatography (0-20% ethyl acetate in cyclohexane)
Sources & evidence
- ORD record
- ord-ba0d3a21608b4910ad7938220c817f95
- Source dataset
- uspto-grants-2016_04
- Patent number
- US09309240B2
Reaction notes
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