2,4-dichloro-6-methylbenzonitrile

反応条件: temp:78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A soln. of 2,4-dichloro-6-methylbenzonitrile (16.9 mmol) in 34 mL chlorobenzene was heated to 50° C. when NBS (18.6 mmol) was added. The flask was purged with Ar before AIBN (1.69 mmol) was added at once still at 50° C. The reaction mixture was then stirred at 78° C. After 2 h and 4 h, another portion of AIBN (1.69 mmol) was added and heating to 78° C. was continued overnight. The solvent was then evaporated off, the resulting residue was redissolved in Et2O and the remaining solid was removed by filtration. The filtrate was washed twice with 2N HCl solution and brine, it was dried over MgSO4 and conc. in vacuo. Purification with CC (0-100% EtOAc/Hept) gives the desired compound as yellowish solid. was added was added at once still at 50° C heating to 78° C. was continued overnight The solvent was then evaporated off the resulting residue was redissolved in Et2O the remaining solid was removed by filtration The filtrate was washed twice with 2N HCl solution and brine, it was dried over MgSO4 and conc. in vacuo Purification with CC (0-100% EtOAc/Hept)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a suspension of sodium hydride (60% suspension in mineral oil, 0.54 g, 13.6 mmol) in dry tetrahydrofuran (15 ml) is added ethanethiol (0.36 ml, 4.84 mmol) at 0° C. After effervescence has ceased, a solution of 2,4-dichloro-6-methyl-benzonitrile (1.00 g, 5.37 mmol) in THF (5 ml) is added drop wise at 0° C. The reaction mixture is stirred at RT for 16 h. After completion of the reaction (monitored by TLC), the reaction is quenched with ice water and extracted with ethyl acetate (3×30 ml). The organic layer is washed with saturated sodium hydrogen carbonate solution (20 ml), water (20 ml), brine (20 ml), dried over anhydrous sodium sulfate and evaporated to get the crude product, which is purified by column chromatography (silica gel, 5% dichloromethane/hexane) to yield 4-chloro-2-ethylsulfanyl-6-methyl-benzonitrile (0.50 g, 2.37 mmol, 44%). After completion of the reaction (monitored by TLC) the reaction is quenched with ice water extracted with ethyl acetate (3×30 ml) The organic layer is washed with saturated sodium hydrogen carbonate solution (20 ml), water (20 ml), brine (20 ml) dried over anhydrous sodium sulfate evaporated to get the crude product, which is purified by column chromatography (silica gel, 5% dichloromethane/hexane)

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 2,4-dichloro-6-methyl-benzonitrile (5.0 g, 26.9 mmol) in DMF (50 ml) in a sealed tube are added tripotassium phosphate (5.7 g, 26.9 mmol) and L-proline (0.62 g, 5.37 mmol) at RT. The reaction mixture is degassed and flushed with argon for 30 min and then are added CuI (0.51 g, 2.68 mmol) and ethanethiol (6.0 ml, 80.6 mmol) at RT. The reaction mixture is stirred at 80° C. for 16 h. After completion of the reaction (monitored by TLC), the reaction mixture is diluted with water (50 ml) and extracted with ethyl acetate (50×3 ml). The organic layer is washed with water (50 ml), brine (15 ml) dried over anhydrous sodium sulfate and evaporated to get the crude which is purified by column chromatography (silica gel, 5% acetone/hexane) to yield 4-chloro-2-ethylsulfanyl-6-methyl-benzonitrile (1.3 g, 6.14 mmol, 23%). The reaction mixture is degassed flushed with argon for 30 min After completion of the reaction (monitored by TLC) extracted with ethyl acetate (50×3 ml) The organic layer is washed with water (50 ml), brine (15 ml) dried over anhydrous sodium sulfate evaporated to get the crude which is purified by column chromatography (silica gel, 5% acetone/hexane)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The preparation takes place in analogy to Example 6A from 2,4-dichloro-6-methylbenzonitrile with subsequent treatment with 4N hydrochloric acid in dioxane.

反応条件: temp:78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 2,4-dichloro-6-methylbenzonitrile (16.9 mmol) in 34 mL chlorobenzene was heated to 50° C. when NBS (18.6 mmol) was added. The flask was purged with Ar before AIBN (1.69 mmol) was added at once still at 50° C. The reaction mixture was then stirred at 78° C. After 2 h and 4 h, another portion of AIBN (1.69 mmol) was added and heating to 78° C. was continued overnight. The solvent was then evaporated off, the resulting residue was redissolved in Et2O and the remaining solid was removed by filtration. The filtrate was washed twice with 2N HCl solution and brine, it was dried over MgSO4 and concentrated in vacuo. Purification with CC (KP-SIL™ from Biotage) using Hept to EtOAc gives the desired compound as yellowish solid. was added was added at once still at 50° C heating to 78° C. was continued overnight The solvent was then evaporated off the resulting residue was redissolved in Et2O the remaining solid was removed by filtration The filtrate was washed twice with 2N HCl solution and brine, it was dried over MgSO4 concentrated in vacuo Purification with CC (KP-SIL™ from Biotage)

反応条件: temp:78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A soln. of 2,4-dichloro-6-methylbenzonitrile (16.9 mmol) in 34 mL chlorobenzene was heated to 50° C. when NBS (18.6 mmol) was added. The flask was purged with Ar before AIBN (1.69 mmol) was added at once still at 50° C. The reaction mixture was then stirred at 78° C. After 2 h and 4 h, another portion of AIBN (1.69 mmol) was added and heating to 78° C. was continued overnight. The solvent was then evaporated off, the resulting residue was redissolved in Et2O and the remaining solid was removed by filtration. The filtrate was washed twice with 2N HCl solution and brine, it was dried over MgSO4 and conc. in vacuo. Purification with CC (0-100% EtOAc/Hept) gives the desired compound as yellowish solid. was added was added at once still at 50° C heating to 78° C. was continued overnight The solvent was then evaporated off the resulting residue was redissolved in Et2O the remaining solid was removed by filtration The filtrate was washed twice with 2N HCl solution and brine, it was dried over MgSO4 and conc. in vacuo Purification with CC (0-100% EtOAc/Hept)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a suspension of sodium hydride (60% suspension in mineral oil, 0.54 g, 13.6 mmol) in dry tetrahydrofuran (15 ml) is added ethanethiol (0.36 ml, 4.84 mmol) at 0° C. After effervescence has ceased, a solution of 2,4-dichloro-6-methyl-benzonitrile (1.00 g, 5.37 mmol) in THF (5 ml) is added drop wise at 0° C. The reaction mixture is stirred at RT for 16 h. After completion of the reaction (monitored by TLC), the reaction is quenched with ice water and extracted with ethyl acetate (3×30 ml). The organic layer is washed with saturated sodium hydrogen carbonate solution (20 ml), water (20 ml), brine (20 ml), dried over anhydrous sodium sulfate and evaporated to get the crude product, which is purified by column chromatography (silica gel, 5% dichloromethane/hexane) to yield 4-chloro-2-ethylsulfanyl-6-methyl-benzonitrile (0.50 g, 2.37 mmol, 44%). After completion of the reaction (monitored by TLC) the reaction is quenched with ice water extracted with ethyl acetate (3×30 ml) The organic layer is washed with saturated sodium hydrogen carbonate solution (20 ml), water (20 ml), brine (20 ml) dried over anhydrous sodium sulfate evaporated to get the crude product, which is purified by column chromatography (silica gel, 5% dichloromethane/hexane)

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 2,4-dichloro-6-methyl-benzonitrile (5.0 g, 26.9 mmol) in DMF (50 ml) in a sealed tube are added tripotassium phosphate (5.7 g, 26.9 mmol) and L-proline (0.62 g, 5.37 mmol) at RT. The reaction mixture is degassed and flushed with argon for 30 min and then are added CuI (0.51 g, 2.68 mmol) and ethanethiol (6.0 ml, 80.6 mmol) at RT. The reaction mixture is stirred at 80° C. for 16 h. After completion of the reaction (monitored by TLC), the reaction mixture is diluted with water (50 ml) and extracted with ethyl acetate (50×3 ml). The organic layer is washed with water (50 ml), brine (15 ml) dried over anhydrous sodium sulfate and evaporated to get the crude which is purified by column chromatography (silica gel, 5% acetone/hexane) to yield 4-chloro-2-ethylsulfanyl-6-methyl-benzonitrile (1.3 g, 6.14 mmol, 23%). The reaction mixture is degassed flushed with argon for 30 min After completion of the reaction (monitored by TLC) extracted with ethyl acetate (50×3 ml) The organic layer is washed with water (50 ml), brine (15 ml) dried over anhydrous sodium sulfate evaporated to get the crude which is purified by column chromatography (silica gel, 5% acetone/hexane)