4-fluoro-3-formylbenzonitrile

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: To a solution of 5-cyano-2-fluorobenzaldehyde (1.50 g, 10.06 mmol) in THF (15 mL) cooled to 0° C. was added methyllithium (7.90 mL, 11.06 mmol). The mixture was stirred at room temperature for 2 h and quenched by the addition of saturated NH4Cl (10 mL). The mixture was partitioned between ethyl acetate (50 mL) and water (20 mL), the organic was washed with water (20 mL), dried over magnesium sulfate and concentrated in vacuo to provide a residue. Purification via flash column chromatography (30×150 mm column; elution with EtOAc: Hex, 1:2) afforded pure compound: quenched by the addition of saturated NH4Cl (10 mL) The mixture was partitioned between ethyl acetate (50 mL) and water (20 mL) the organic was washed with water (20 mL) dried over magnesium sulfate concentrated in vacuo to provide a residue Purification via flash column chromatography (30×150 mm column; elution with EtOAc: Hex, 1:2) afforded pure compound

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

Procedure: 5-Cyano-2-fluorobenzaldehyde (512 mg, 3.43 mmol) was dissolved in hydrazine hydrate (25 mL) at room temperature and the solution left to stand overnight. To this reaction mixture was added methylene chloride (30 mL). The mixture was purified by filtration through a pad of silica eluting with methylene chloride, concentrated in vacuo to afford a white solid: the solution left The mixture was purified by filtration through a pad of silica eluting with methylene chloride concentrated in vacuo to afford a white solid

Conditions: temp:190.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 5-bromo-2-fluorobenzaldehyde (1.93 g, 9.51 mmol) in DMF (4 mL) was added copper(I) cyanide (0.98 g, 10.93 mmol). The mixture was heated to 190° C. and stirred for 5 h. The dark brown reaction mixture was poured into a solution containing ferric chloride (3.0 g), conc. HCl (0.93 mL) and water (6 mL) and warmed to 65° C. for 20 min. The mixture was partitioned between toluene (20 mL) and water (20 mL). The organic was washed with diluted HCl (25 mL), water (20 mL), 10% sodium hydroxide (25 mL), dried over magnesium sulfate, and concentrated to provide a solid product: The dark brown reaction mixture was poured into a solution warmed to 65° C. for 20 min The mixture was partitioned between toluene (20 mL) and water (20 mL) The organic was washed with diluted HCl (25 mL), water (20 mL), 10% sodium hydroxide (25 mL) dried over magnesium sulfate concentrated to provide a solid product

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

Procedure: To a stirred, cooled solution (0° C.) of diisopropylamine (15.4 mL, 0.11 mol) in anhydrous tetrahydrofuran (200 mL) n-butyllithium (40 mL of 2.5M in hexane, 0.11 mol) was added from a dropping funnel over a period of 30 min. under argon. The mixture was stirred at that temperature for 30 min. and then cooled to −78° C. A solution of 4-fluoro-benzonitrile (12.1g, 0.1 mol) in dry THF (50 mL) was then added dropwise over 15 min. via syringe and stirred for 1 hour at −78° C. Dimethylformamide (8 mL) was added dropwise from a syringe and the stirring was continued for another 20 min. The reaction was quenched by the rapid addition of acetic acid (20 mL) followed by water (500 mL) and the product was extracted with diethyl ether (2×500 mL). The combined organic layers were washed with 1N HCl, water, saturated sodium chloride and then dried over anhydrous magnesium sulfate, and evaporated to give 2-fluoro-5-cyano-benzaldehyde (11.8 g, 79% yield) as a light yellow solid. was added from a dropping funnel over a period of 30 min. under argon stirred for 1 hour at −78° C the stirring was continued for another 20 min The reaction was quenched by the rapid addition of acetic acid (20 mL) the product was extracted with diethyl ether (2×500 mL) The combined organic layers were washed with 1N HCl, water, saturated sodium chloride dried over anhydrous magnesium sulfate evaporated

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir: