2-chloro-6-ethylbenzaldehyde

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

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

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 1.60 ml (9.79 mmol) 1-(diethoxymethyl)imidazole in 6 ml tetrahydrofuran at −78° C. was added dropwise 6.67 ml (10.7 mmol) of a 1.6 M solution of n-butyllithium in hexane. The resulting solution of 2-(1-diethoxymethyl-1H-imidazol-2-yl)-lithium was stirred at −78° C., and then added dropwise to a solution of 1.50 g (8.90 mmol) 2-chloro-6-ethyl-benzaldehyde in 6 ml tetrahydrofuran at 0° C. The reaction mixture was then stirred at 0° C. for 30 min and at room temperature for 1 h, before being quenched by dropwise addition of 1 M aqueous hydrochloric acid. The mixture was made basic by addition of aqueous sodium bicarbonbate solution and diluted with ethyl acetate. The phases were separated and the organic phase was washed with saturated brine, dried over Na2SO4, filtered and concentrated in vacuo to afford 2.02 g (96%) of the title compound as a yellow oil which was used in the next step without further purification. before being quenched by dropwise addition of 1 M aqueous hydrochloric acid The mixture was made basic by addition of aqueous sodium bicarbonbate solution diluted with ethyl acetate The phases were separated the organic phase was washed with saturated brine dried over Na2SO4 filtered concentrated in vacuo

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 1.60 ml (9.79 mmol) 1-(diethoxymethyl)imidazole in 6 ml tetrahydrofuran at −78° C. was added dropwise 6.67 ml (10.7 mmol) of a 1.6 M solution of n-butyllithium in hexane. The resulting solution of 2-(1-diethoxymethyl-1H-imidazol-2-yl)-lithium was stirred at −78° C., and then added dropwise to a solution of 1.50 g (8.90 mmol) 2-chloro-6-ethyl-benzaldehyde in 6 ml tetrahydrofuran at 0° C. The reaction mixture was then stirred at 0° C. for 30 min and at room temperature for 1 h, before being quenched by dropwise addition of 1 M aqueous hydrochloric acid. The mixture was made basic by addition of aqueous sodium bicarbonbate solution and diluted with ethyl acetate. The phases were separated and the organic phase was washed with saturated brine, dried over Na2SO4, filtered and concentrated in vacuo to afford 2.02 g (96%) of the title compound as a yellow oil which was used in the next step without further purification. before being quenched by dropwise addition of 1 M aqueous hydrochloric acid The mixture was made basic by addition of aqueous sodium bicarbonbate solution diluted with ethyl acetate The phases were separated the organic phase was washed with saturated brine dried over Na2SO4 filtered concentrated in vacuo

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

Procedure: To a solution of 19.7 g (88.1 mmol) butyl-[1-(2-chloro-6-ethyl-phenyl)-meth-(E)-ylidene]-amine in 70 ml water at 0° C. was added dropwise 18.9 ml concentrated sulphuric acid. The mixture was then heated at reflux for 90 min before being cooled to room temperature and diluted with ethyl acetate. The mixture was then washed sequentially with water, saturated aqueous sodium bicarbonate solution, and saturated brine. The organic phase was dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by flash chromatography (silica gel, ethyl acetate/heptane 1:30) to afford 11.4 g (77%) of the title compound as a yellow oil. 1H-NMR (CDCl3): 1.22 (3H, t, CH3), 2.97 (2H, q, CH2), 7.20 (1H, d, ArH), 7.30 (1H, d, ArH), 7.39 (1H, dd, ArH), 10.65 (1H, s, CHO). The mixture was then heated at reflux for 90 min The mixture was then washed sequentially with water, saturated aqueous sodium bicarbonate solution, and saturated brine The organic phase was dried over Na2SO4 filtered concentrated in vacuo The residue was purified by flash chromatography (silica gel, ethyl acetate/heptane 1:30)

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

Procedure: To a solution of 19.7 g (88.1 mmol) butyl-[1-(2-chloro-6-ethyl-phenyl)-meth-(E)-ylidene]-amine in 70 ml water at 0° C. was added dropwise 18.9 ml concentrated sulphuric acid. The mixture was then heated at reflux for 90 min before being cooled to room temperature and diluted with ethyl acetate. The mixture was then washed sequentially with water, saturated aqueous sodium bicarbonate solution, and saturated brine. The organic phase was dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by flash chromatography (silica gel, ethyl acetate/heptane 1:30) to afford 11.4 g (77%) of the title compound as a yellow oil. 1H-NMR (CDCl3): 1.22 (3H, t, CH3), 2.97 (2H, q, CH2), 7.20 (1H, d, ArH), 7.30 (1H, d, ArH), 7.39 (1H, dd, ArH), 10.65 (1H, s, CHO). The mixture was then heated at reflux for 90 min The mixture was then washed sequentially with water, saturated aqueous sodium bicarbonate solution, and saturated brine The organic phase was dried over Na2SO4 filtered concentrated in vacuo The residue was purified by flash chromatography (silica gel, ethyl acetate/heptane 1:30)

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

Procedure: To a room temperature suspension of 2-chloro-6-ethylbenzaldehyde (13.5 mmol, 2.27 g) in acetonitrile (25 mL) was added a solution of monobasic sodium phosphate (3.4 mmol, 0.465 g) in water (7.5 mL) followed by hydrogen peroxide (1.8 mL, 30%). Then, a solution of sodium chlorite (23.7 mmol, 2.15 g) in water (20 mL) was added dropwise at 0° C. while maintaining the temperature below 3° C. After addition, the yellow suspension was stirred for 15 h at 0° C. to room temperature. At this time TLC analysis of the mixture indicated the absence of starting material. Then, a solution of sodium bisulfite (20.5 mmol, 2.8 g) in water (10 mL) was added dropwise at 0° C. until the yellow color disappeared (KI-paper positive). Cooling is essential to control the exothermic reaction. After 1 h, the solvent was removed under vacuum. The neutral impurities were extracted with diethyl ether (200 mL). Then, the basic aqueous solution was neutralized with 10% HCl to pH ˜1. The precipitated white solid was collected by filtration and dried at in air to afford 2.415 g (97% yield) of 2-chloro-6-ethylbenzoic acid as an amorphous white solid. EI-HRMS m/e calcd for C9H9ClO2 (M+) 184.0291, found 184.0295. while maintaining the temperature below 3° C After addition Cooling the exothermic reaction After 1 h the solvent was removed under vacuum The neutral impurities were extracted with diethyl ether (200 mL) The precipitated white solid was collected by filtration dried at in air

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

Procedure: To a room temperature suspension of 2-chloro-6-ethylbenzaldehyde (13.5 mmol, 2.27 g) in acetonitrile (25 mL) was added a solution of monobasic sodium phosphate (3.4 mmol, 0.465 g) in water (7.5 mL) followed by hydrogen peroxide (1.8 mL, 30%). Then, a solution of sodium chlorite (23.7 mmol, 2.15 g) in water (20 mL) was added dropwise at 0° C. while maintaining the temperature below 3° C. After addition, the yellow suspension was stirred for 15 h at 0° C. to room temperature. At this time TLC analysis of the mixture indicated the absence of starting material. Then, a solution of sodium bisulfite (20.5 mmol, 2.8 g) in water (10 mL) was added dropwise at 0° C. until the yellow color disappeared (KI-paper positive). Cooling is essential to control the exothermic reaction. After 1 h, the solvent was removed under vacuum. The neutral impurities were extracted with diethyl ether (200 mL). Then, the basic aqueous solution was neutralized with 10% HCl to pH ˜1. The precipitated white solid was collected by filtration and dried at in air to afford 2.415 g (97% yield) of 2-chloro-6-ethylbenzoic acid as an amorphous white solid. EI-HRMS m/e calcd for C9H9ClO2 (M+) 184.0291, found 184.0295. while maintaining the temperature below 3° C After addition Cooling the exothermic reaction After 1 h the solvent was removed under vacuum The neutral impurities were extracted with diethyl ether (200 mL) The precipitated white solid was collected by filtration dried at in air

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 1.60 ml (9.79 mmol) 1-(diethoxymethyl)imidazole in 6 ml tetrahydrofuran at −78° C. was added dropwise 6.67 ml (10.7 mmol) of a 1.6 M solution of n-butyllithium in hexane. The resulting solution of 2-(1-diethoxymethyl-1H-imidazol-2-yl)-lithium was stirred at −78° C., and then added dropwise to a solution of 1.50 g (8.90 mmol) 2-chloro-6-ethyl-benzaldehyde in 6 ml tetrahydrofuran at 0° C. The reaction mixture was then stirred at 0° C. for 30 min and at room temperature for 1 h, before being quenched by dropwise addition of 1 M aqueous hydrochloric acid. The mixture was made basic by addition of aqueous sodium bicarbonbate solution and diluted with ethyl acetate. The phases were separated and the organic phase was washed with saturated brine, dried over Na2SO4, filtered and concentrated in vacuo to afford 2.02 g (96%) of the title compound as a yellow oil which was used in the next step without further purification. before being quenched by dropwise addition of 1 M aqueous hydrochloric acid The mixture was made basic by addition of aqueous sodium bicarbonbate solution diluted with ethyl acetate The phases were separated the organic phase was washed with saturated brine dried over Na2SO4 filtered concentrated in vacuo

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

Procedure: To a solution of 19.7 g (88.1 mmol) butyl-[1-(2-chloro-6-ethyl-phenyl)-meth-(E)-ylidene]-amine in 70 ml water at 0° C. was added dropwise 18.9 ml concentrated sulphuric acid. The mixture was then heated at reflux for 90 min before being cooled to room temperature and diluted with ethyl acetate. The mixture was then washed sequentially with water, saturated aqueous sodium bicarbonate solution, and saturated brine. The organic phase was dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by flash chromatography (silica gel, ethyl acetate/heptane 1:30) to afford 11.4 g (77%) of the title compound as a yellow oil. 1H-NMR (CDCl3): 1.22 (3H, t, CH3), 2.97 (2H, q, CH2), 7.20 (1H, d, ArH), 7.30 (1H, d, ArH), 7.39 (1H, dd, ArH), 10.65 (1H, s, CHO). The mixture was then heated at reflux for 90 min The mixture was then washed sequentially with water, saturated aqueous sodium bicarbonate solution, and saturated brine The organic phase was dried over Na2SO4 filtered concentrated in vacuo The residue was purified by flash chromatography (silica gel, ethyl acetate/heptane 1:30)

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

Procedure: To a solution of 19.7 g (88.1 mmol) butyl-[1-(2-chloro-6-ethyl-phenyl)-meth-(E)-ylidene]-amine in 70 ml water at 0° C. was added dropwise 18.9 ml concentrated sulphuric acid. The mixture was then heated at reflux for 90 min before being cooled to room temperature and diluted with ethyl acetate. The mixture was then washed sequentially with water, saturated aqueous sodium bicarbonate solution, and saturated brine. The organic phase was dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by flash chromatography (silica gel, ethyl acetate/heptane 1:30) to afford 11.4 g (77%) of the title compound as a yellow oil. 1H-NMR (CDCl3): 1.22 (3H, t, CH3), 2.97 (2H, q, CH2), 7.20 (1H, d, ArH), 7.30 (1H, d, ArH), 7.39 (1H, dd, ArH), 10.65 (1H, s, CHO). The mixture was then heated at reflux for 90 min The mixture was then washed sequentially with water, saturated aqueous sodium bicarbonate solution, and saturated brine The organic phase was dried over Na2SO4 filtered concentrated in vacuo The residue was purified by flash chromatography (silica gel, ethyl acetate/heptane 1:30)

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

Procedure: To a room temperature suspension of 2-chloro-6-ethylbenzaldehyde (13.5 mmol, 2.27 g) in acetonitrile (25 mL) was added a solution of monobasic sodium phosphate (3.4 mmol, 0.465 g) in water (7.5 mL) followed by hydrogen peroxide (1.8 mL, 30%). Then, a solution of sodium chlorite (23.7 mmol, 2.15 g) in water (20 mL) was added dropwise at 0° C. while maintaining the temperature below 3° C. After addition, the yellow suspension was stirred for 15 h at 0° C. to room temperature. At this time TLC analysis of the mixture indicated the absence of starting material. Then, a solution of sodium bisulfite (20.5 mmol, 2.8 g) in water (10 mL) was added dropwise at 0° C. until the yellow color disappeared (KI-paper positive). Cooling is essential to control the exothermic reaction. After 1 h, the solvent was removed under vacuum. The neutral impurities were extracted with diethyl ether (200 mL). Then, the basic aqueous solution was neutralized with 10% HCl to pH ˜1. The precipitated white solid was collected by filtration and dried at in air to afford 2.415 g (97% yield) of 2-chloro-6-ethylbenzoic acid as an amorphous white solid. EI-HRMS m/e calcd for C9H9ClO2 (M+) 184.0291, found 184.0295. while maintaining the temperature below 3° C After addition Cooling the exothermic reaction After 1 h the solvent was removed under vacuum The neutral impurities were extracted with diethyl ether (200 mL) The precipitated white solid was collected by filtration dried at in air