2-chloro-4-methylbenzonitrile

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

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

Conditions: temp:105.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-chloro-4methylbenzonitrile (2.00 g, 13.19 mmol) in toluene (25 ml), was prepared at room temperature and 3M bromo methyl magnesium (13.2 ml, 39.68 mmol) in diethylether, 3M was added dropwise and the mixture then heated to reflux (100-110° C.) for 16 h. The mixture was then cooled to 0° C. and then adjusted to pH 2 with 2M aqueous HCl. The mixture was then heated to reflux as above for 2 h. The mixture was then basified with 2M NaOH to pH 11, extracted with EtOAc (100 ml), the organic phase dried over MgSO4 and then concentrated under reduced pressure. The crude product was then purified by column chromatography (0-10% EtOAc/Hexanes) to afford 1-(2-chloro-4-methylphenyl)ethanone as a pale yellow oil (1.60 g, 9.50 mmol, 72%). was prepared at room temperature the mixture then heated The mixture was then cooled to 0° C. The mixture was then heated to reflux as above for 2 h extracted with EtOAc (100 ml) the organic phase dried over MgSO4 concentrated under reduced pressure The crude product was then purified by column chromatography (0-10% EtOAc/Hexanes)

Conditions: temp:105.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-chloro-4methylbenzonitrile (2.00 g, 13.19 mmol) in toluene (25 ml), was prepared at room temperature and 3M bromo methyl magnesium (13.2 ml, 39.68 mmol) in diethylether, 3M was added dropwise and the mixture then heated to reflux (100-110° C.) for 16 h. The mixture was then cooled to 0° C. and then adjusted to pH 2 with 2M aqueous HCl. The mixture was then heated to reflux as above for 2 h. The mixture was then basified with 2M NaOH to pH 11, extracted with EtOAc (100 ml), the organic phase dried over MgSO4 and then concentrated under reduced pressure. The crude product was then purified by column chromatography (0-10% EtOAc/Hexanes) to afford 1-(2-chloro-4-methylphenyl)ethanone as a pale yellow oil (1.60 g, 9.50 mmol, 72%). was prepared at room temperature the mixture then heated The mixture was then cooled to 0° C. The mixture was then heated to reflux as above for 2 h extracted with EtOAc (100 ml) the organic phase dried over MgSO4 concentrated under reduced pressure The crude product was then purified by column chromatography (0-10% EtOAc/Hexanes)

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

Procedure: A mixture of 2-chloro-4-methylbenzonitrile (5.5 g, 36.28 mmol), conc. sulfuric acid (30 mL) and ethanol (30 mL) was heated under reflux for 22 hr. The reaction mixture was ice-cooled, and neutralized with 8N aqueous sodium hydroxide solution, and ethanol was evaporated. The residue was extracted with ethyl acetate, and the extract was washed with brine, dried over magnesium sulfate and concentrated under reduced pressure. The residue was diluted with ethyl acetate-hexane (1:10, 120 mL). The insoluble material was filtered off, and the filtrate was under reduced pressure and concentrated to give the title compound (3.23 g, 45%) as a pale-brown liquid. was heated under reflux for 22 hr cooled was evaporated The residue was extracted with ethyl acetate the extract was washed with brine dried over magnesium sulfate concentrated under reduced pressure The residue was diluted with ethyl acetate-hexane (1:10, 120 mL) The insoluble material was filtered off concentrated

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

Procedure: A mixture of 2-chloro-4-methylbenzonitrile (5.5 g, 36.28 mmol), conc. sulfuric acid (30 mL) and ethanol (30 mL) was heated under reflux for 22 hr. The reaction mixture was ice-cooled, and neutralized with 8N aqueous sodium hydroxide solution, and ethanol was evaporated. The residue was extracted with ethyl acetate, and the extract was washed with brine, dried over magnesium sulfate and concentrated under reduced pressure. The residue was diluted with ethyl acetate-hexane (1:10, 120 mL). The insoluble material was filtered off, and the filtrate was under reduced pressure and concentrated to give the title compound (3.23 g, 45%) as a pale-brown liquid. was heated under reflux for 22 hr cooled was evaporated The residue was extracted with ethyl acetate the extract was washed with brine dried over magnesium sulfate concentrated under reduced pressure The residue was diluted with ethyl acetate-hexane (1:10, 120 mL) The insoluble material was filtered off concentrated

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

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

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 4-methyl-2-chlorobenzonitrile (1.51 g, 10 mmol), N-bromosuccinimide (2.14 g, 12.0 mmol) and AIBN (33 mg, 0.20 mmol) in ACN (40 mL) was heated under reflux for 18 hours. The reaction mixture was diluted with EtOAc and washed with a saturated aqueous solution of Na2CO3 and brine. The organic layer was dried (MgSO4) and concentrated under vacuum. The residue was treated with sarcosine tert-butyl ester hydrochloride (1.44 g, 7.92 mmol) and K2CO3 (2.74 g, 19.8 mmol) in ACN (10 mL). The mixture was heated at 100° C. for 2 hours. The solvent was evaporated under vacuum. The residue was dissolved in a mixture of DCM and water and then poured through a hydrophobic frit. The solvent was evaporated under vacuum. The residue was purified by flash chromatography (silica, iso-hexane/Et2O) to afford the title compound (1.95 g, quantitative). 1H NMR (CDCl3, 400 MHz) δ 7.61 (1H, d, J=8.0 Hz), 7.57 (1H, s), 7.36 (1H, m), 3.73 (2H, s), 3.21 (2H, s), 2.36 (3H, s), 1.48 (9H, s). under reflux for 18 hours washed with a saturated aqueous solution of Na2CO3 and brine The organic layer was dried (MgSO4) concentrated under vacuum The solvent was evaporated under vacuum The residue was dissolved in a mixture of DCM and water poured through a hydrophobic frit The solvent was evaporated under vacuum The residue was purified by flash chromatography (silica, iso-hexane/Et2O)

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 4-methyl-2-chlorobenzonitrile (1.51 g, 10 mmol), N-bromosuccinimide (2.14 g, 12.0 mmol) and AIBN (33 mg, 0.20 mmol) in ACN (40 mL) was heated under reflux for 18 hours. The reaction mixture was diluted with EtOAc and washed with a saturated aqueous solution of Na2CO3 and brine. The organic layer was dried (MgSO4) and concentrated under vacuum. The residue was treated with sarcosine tert-butyl ester hydrochloride (1.44 g, 7.92 mmol) and K2CO3 (2.74 g, 19.8 mmol) in ACN (10 mL). The mixture was heated at 100° C. for 2 hours. The solvent was evaporated under vacuum. The residue was dissolved in a mixture of DCM and water and then poured through a hydrophobic frit. The solvent was evaporated under vacuum. The residue was purified by flash chromatography (silica, iso-hexane/Et2O) to afford the title compound (1.95 g, quantitative). 1H NMR (CDCl3, 400 MHz) δ 7.61 (1H, d, J=8.0 Hz), 7.57 (1H, s), 7.36 (1H, m), 3.73 (2H, s), 3.21 (2H, s), 2.36 (3H, s), 1.48 (9H, s). under reflux for 18 hours washed with a saturated aqueous solution of Na2CO3 and brine The organic layer was dried (MgSO4) concentrated under vacuum The solvent was evaporated under vacuum The residue was dissolved in a mixture of DCM and water poured through a hydrophobic frit The solvent was evaporated under vacuum The residue was purified by flash chromatography (silica, iso-hexane/Et2O)

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 4-methyl-2-chlorobenzonitrile (1.51 g, 10 mmol), N-bromosuccinimide (2.14 g, 12.0 mmol) and AIBN (33 mg, 0.20 mmol) in ACN (40 mL) was heated under reflux for 18 hours. The reaction mixture was diluted with EtOAc and washed with a saturated aqueous solution of Na2CO3 and brine. The organic layer was dried (MgSO4) and concentrated under vacuum. The residue was treated with sarcosine tert-butyl ester hydrochloride (1.44 g, 7.92 mmol) and K2CO3 (2.74 g, 19.8 mmol) in ACN (10 mL). The mixture was heated at 100° C. for 2 hours. The solvent was evaporated under vacuum. The residue was dissolved in a mixture of DCM and water and then poured through a hydrophobic frit. The solvent was evaporated under vacuum. The residue was purified by flash chromatography (silica, iso-hexane/Et2O) to afford the title compound (1.95 g, quantitative). 1H NMR (CDCl3, 400 MHz) δ 7.61 (1H, d, J=8.0 Hz), 7.57 (1H, s), 7.36 (1H, m), 3.73 (2H, s), 3.21 (2H, s), 2.36 (3H, s), 1.48 (9H, s). under reflux for 18 hours washed with a saturated aqueous solution of Na2CO3 and brine The organic layer was dried (MgSO4) concentrated under vacuum The solvent was evaporated under vacuum The residue was dissolved in a mixture of DCM and water poured through a hydrophobic frit The solvent was evaporated under vacuum The residue was purified by flash chromatography (silica, iso-hexane/Et2O)

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 4-methyl-2-chlorobenzonitrile (1.51 g, 10 mmol), N-bromosuccinimide (2.14 g, 12.0 mmol) and AIBN (33 mg, 0.20 mmol) in ACN (40 mL) was heated under reflux for 18 hours. The reaction mixture was diluted with EtOAc and washed with a saturated aqueous solution of Na2CO3 and brine. The organic layer was dried (MgSO4) and concentrated under vacuum. The residue was treated with sarcosine tert-butyl ester hydrochloride (1.44 g, 7.92 mmol) and K2CO3 (2.74 g, 19.8 mmol) in ACN (10 mL). The mixture was heated at 100° C. for 2 hours. The solvent was evaporated under vacuum. The residue was dissolved in a mixture of DCM and water and then poured through a hydrophobic frit. The solvent was evaporated under vacuum. The residue was purified by flash chromatography (silica, iso-hexane/Et2O) to afford the title compound (1.95 g, quantitative). 1H NMR (CDCl3, 400 MHz) δ 7.61 (1H, d, J=8.0 Hz), 7.57 (1H, s), 7.36 (1H, m), 3.73 (2H, s), 3.21 (2H, s), 2.36 (3H, s), 1.48 (9H, s). under reflux for 18 hours washed with a saturated aqueous solution of Na2CO3 and brine The organic layer was dried (MgSO4) concentrated under vacuum The solvent was evaporated under vacuum The residue was dissolved in a mixture of DCM and water poured through a hydrophobic frit The solvent was evaporated under vacuum The residue was purified by flash chromatography (silica, iso-hexane/Et2O)