2-fluoro-4-prop-2-enylbenzonitrile

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Fluoro-4-[2-(piperazin-1yl)ethyl]benzonitrile was prepared from 2-fluoro-4-(prop-2-en-1-yl)benzonitrile (described above) in an analogous fashion to that described for 2-methoxy-4-[2-(piperazin-1-yl)ethyl]benzonitrile.

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 4-allyl-2-fluorobenzonitrile (1 g, 6.2 mmol) in 1:1 CH2Cl2/MeOH (40 mL) containing pyridine (1 mL, 12.4 mmol) was cooled to −78° C., and O3 was passed through until a blue color was present. N2 was then bubbled through to discharge the blue color and Me2S (5 ml) was added. The reaction mixture was allowed to warm and left overnight. The mixture was washed with 1 N HCl and aqueous NaHCO3 and then dried and concentrated to give crude 2-fluoro-4-(2-oxoethyl)benzonitrile. The material was carried on as the crude. N2 was then bubbled through was added to warm The mixture was washed with 1 N HCl and aqueous NaHCO3 dried concentrated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-bromo-2-fluorobenzonitrile (5.0 g, 13 mmol) in 100 ml of toluene was added LiCl (1.7 g, 39 mmol), Pd(PPh3)4 (400 mg), Allyl tributyltin (5.2 g, 16 mmol), and then the mixture was heated to reflux overnight. After the reaction was completed, the reaction solution was diluted with EtOAc and filtered. The filtrate was concentrated and purified with silica gel column chromatograph to give crude 4-allyl-2-fluorobenzonitrile. the mixture was heated to reflux overnight filtered The filtrate was concentrated purified with silica gel column chromatograph

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-allyl-2-fluorobenzonitrile (1.3 g, 8.1 mmol) in 30 mL of methanol and 10 mL of water was added OsO4 (200 mg) and NMO (2.7 g, 20 mmol), and the mixture was stirred at ambient temperature overnight. Remove the methanol under reduced pressure, the residue was dissolved in EtOAc, washed with brine, dried over anhydrous sodium sulfate and concentrated. The residue was purified by fast column chromatograph to give 4-(2,3-dihydroxypropyl)-2-fluorobenzonitrile. MS m/z: 196 (M+1)+. Remove the methanol under reduced pressure the residue was dissolved in EtOAc washed with brine dried over anhydrous sodium sulfate concentrated The residue was purified by fast column chromatograph

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 4-bromo-2-fluorobenzonitrile (250 mg, 1.3 mmol), allyl-tributyl-stannane (500 mg, 1.5 mmol), LiCl (160 mg, 3.8 mmol) and Pd(PPh)4 (15 mg) in 5 mL of anhydrous toluene was refluxed under N2 overnight. Checked the reaction with TLC and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to give the product 4-allyl-2-fluorobenzonitrile. MS m/z: 162 (M+1)+. was refluxed under N2 overnight Checked the reaction with TLC concentrated under reduced pressure The residue was purified by silica gel column chromatography