5-fluoro-2-methylbenzonitrile

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: A mixture of 5-fluoro-2-methylbenzonitrile (10.0 g, 74.0 mmol), N-bromosuccinimide (NBS, 13.2 g, 74.0 mmol), benzoyl peroxide (0.2 g, 0.82 mmol), and carbon tetrachloride (100 mL) was refluxed for 18 h. The reaction mixture was then cooled to room temperature and filtered through fritted glass. The solid in the funnel was washed with carbon tetrachloride (3×50 mL) and evaporated to dryness under vacuum to provide 16.1 g, 102% yield of product. was refluxed for 18 h filtered through fritted glass The solid in the funnel was washed with carbon tetrachloride (3×50 mL) evaporated to dryness under vacuum

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

Procedure: N2 was passed through a mixture of 5-fluoro-2-methylbenzonitrile (28.51 g, 211 mmol), NBS (41.31 g, 232 mmol) and AIBN (2.5 g, 15 mmol) in CCl4 (845 mL) for 10 min after which the reaction was heated at reflux for 8 h. After standing at room temperature overnight, the reaction mixture was filtered and the filter cake washed with CCl4 (500 mL). The combined filtrate was evaporated to give a yellow oil. Flash chromatography (SiO2) using 5–25% ethyl acetate/Hexanes as eluent afforded the title compound (29.74 g, 66% yield) as a pale yellow oil. 1H NMR (500 MHz, CDCl3) δ: 7.55 (1H, dd, J=8.6, 5.2 Hz), 7.37 (1H, dd, J=7.9, 2.8 Hz), 7.32–7.28 (1H, m), 4.61 (2H, s). was heated at reflux for 8 h the reaction mixture was filtered the filter cake washed with CCl4 (500 mL) The combined filtrate was evaporated to give a yellow oil

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

Procedure: A mixture of 5-fluoro-2-methylbenzonitrile (10.0 g, 74.0 mmol), N-bromosuccinimide (NMS, 13.2 g, 74.0 mmol), benzoyl peroxide (0.2 g, 0.82 mmol), and carbon tetrachloride (100 mL) was refluxed for 18 h. The reaction mixture was then cooled to room temperature and filtered through fritted glass. The solid in the funnel was washed with carbon tetrachloride (3×50 mL) and evaporated to dryness under vacuum to provide 16.1 g, 102% yield of product. was refluxed for 18 h filtered through fritted glass The solid in the funnel was washed with carbon tetrachloride (3×50 mL) evaporated to dryness under vacuum

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

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

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

Procedure: n-Butyllithium (1.40M in hexanes, 11.8 mmol, 8.44 ml) was added dropwise to a stirred solution of diisopropylamine (1.84 ml) in THF (5 ml) at 0° C. After 30 min., the solution was cooled to -78° C. and 3-fluoro-6-methylbenzonitrile (1.60 g, 11.8 mmol) in THF (5 ml) was added dropwise. The pale purple anion was stirred for 20 min., trimethylsilylchoride (3.0 ml, 24 mmol) was added and the mixture warmed to room temperature over 1 h, evaporated, the residue taken up in a small amount of diethyl ether and filtered. Evaporation of the filtrate gave an off-white crystalline solid (2.3 g), m.p. 71-73° C. the mixture warmed to room temperature over 1 h evaporated filtered Evaporation of the filtrate

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

Procedure: n-Butyllithium (1.40M in hexanes, 11.8 mmol, 8.44 ml) was added dropwise to a stirred solution of diisopropylamine (1.84 ml) in THF (5 ml) at 0° C. After 30 min., the solution was cooled to -78° C. and 3-fluoro-6-methylbenzonitrile (1.60 g, 11.8 mmol) in THF (5 ml) was added dropwise. The pale purple anion was stirred for 20 min., trimethylsilylchoride (3.0 ml, 24 mmol) was added and the mixture warmed to room temperature over 1 h, evaporated, the residue taken up in a small amount of diethyl ether and filtered. Evaporation of the filtrate gave an off-white crystalline solid (2.3 g), m.p. 71-73° C. the mixture warmed to room temperature over 1 h evaporated filtered Evaporation of the filtrate

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

Procedure: A mixture of 5-fluoro-2-methylbenzonitrile (10.0 g, 74.0 mmol), N-bromosuccinimide (NBS, 13.2 g, 74.0 mmol), benzoyl peroxide (0.2 g, 0.82 mmol), and carbon tetrachloride (100 mL) was refluxed for 18 h. The reaction mixture was then cooled to room temperature and filtered through fritted glass. The solid in the funnel was washed with carbon tetrachloride (3×50 mL) and evaporated to dryness under vacuum to provide 16.1 g, 102% yield of product. was refluxed for 18 h filtered through fritted glass The solid in the funnel was washed with carbon tetrachloride (3×50 mL) evaporated to dryness under vacuum

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

Procedure: A mixture of 5-fluoro-2-methylbenzonitrile (10.0 g, 74.0 mmol), N-bromosuccinimide (NBS, 13.2 g, 74.0 mmol), benzoyl peroxide (0.2 g, 0.82 mmol), and carbon tetrachloride (100 mL) was refluxed for 18 h. The reaction mixture was then cooled to room temperature and filtered through fritted glass. The solid in the funnel was washed with carbon tetrachloride (3×50 mL) and evaporated to dryness under vacuum to provide 16.1 g, 102% yield of product. was refluxed for 18 h filtered through fritted glass The solid in the funnel was washed with carbon tetrachloride (3×50 mL) evaporated to dryness under vacuum

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

Procedure: N2 was passed through a mixture of 5-fluoro-2-methylbenzonitrile (28.51 g, 211 mmol), NBS (41.31 g, 232 mmol) and AIBN (2.5 g, 15 mmol) in CCl4 (845 mL) for 10 min after which the reaction was heated at reflux for 8 h. After standing at room temperature overnight, the reaction mixture was filtered and the filter cake washed with CCl4 (500 mL). The combined filtrate was evaporated to give a yellow oil. Flash chromatography (SiO2) using 5–25% ethyl acetate/Hexanes as eluent afforded the title compound (29.74 g, 66% yield) as a pale yellow oil. 1H NMR (500 MHz, CDCl3) δ: 7.55 (1H, dd, J=8.6, 5.2 Hz), 7.37 (1H, dd, J=7.9, 2.8 Hz), 7.32–7.28 (1H, m), 4.61 (2H, s). was heated at reflux for 8 h the reaction mixture was filtered the filter cake washed with CCl4 (500 mL) The combined filtrate was evaporated to give a yellow oil