5-bromo-2-chloro-4-methyl-1-oxidopyridin-1-ium

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 5-bromo-2-chloro-4-methylpyridine 1-oxide (from step 1) (1.0 eq.) in acetonitrile (0.2 M) was added TMSCN (4.0 eq.) and triethylamine (3.0 eq.). The reaction was heated at 100° C. overnight. After cooling to room temperature, the solvent was concentrated en vacuo, and the residue was purified by a COMBIFLASH® system (ISCO) using 0-50% ethyl acetate in hexane to give 3-bromo-6-chloro-4-methylpicolinonitrile. After cooling to room temperature the solvent was concentrated en vacuo the residue was purified by a COMBIFLASH® system (ISCO)

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

実験手順: A solution of 5-bromo-2-chloro-4-methylpyridine (1.0 eq.) and meta-chloroperbenzoic acid (mCPBA) (2.5 eq.) in chloroform (0.1 M) was stirred at 50° C. overnight. After cooling to room temperature, Ca(OH)2 (2.5 eq.) was added to the reaction mixture. The precipitate was filtered and washed with 5% methanol in dichloromethane and ethyl acetate. The filtrate was washed with saturated aqueous Na2S2O3 solution and saturated aqueous NaHCO3 solution. The combined organic layers were washed with brine, dried over anhydrous MgSO4, and concentrated en vacuo into a pale solid that was carried onto the next step without further purification. The precipitate was filtered washed with 5% methanol in dichloromethane and ethyl acetate The filtrate was washed with saturated aqueous Na2S2O3 solution and saturated aqueous NaHCO3 solution The combined organic layers were washed with brine dried over anhydrous MgSO4 concentrated en vacuo into a pale solid that was carried onto the next step without further purification

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 5-bromo-2-chloro-4-methylpyridine 1-oxide (from step 1) (1.0 eq.) in acetonitrile (0.2 M) was added TMSCN (4.0 eq.) and triethylamine (3.0 eq.). The reaction was heated at 100° C. overnight. After cooling to room temperature, the solvent was concentrated en vacuo, and the residue was purified by a COMBIFLASH® system (ISCO) using 0-50% ethyl acetate in hexane to give 3-bromo-6-chloro-4-methylpicolinonitrile. After cooling to room temperature the solvent was concentrated en vacuo the residue was purified by a COMBIFLASH® system (ISCO)

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 5-bromo-2-chloro-4-methylpyridine 1-oxide (from step 1) (1.0 eq.) in acetonitrile (0.2 M) was added TMSCN (4.0 eq.) and triethylamine (3.0 eq.). The reaction was heated at 100° C. overnight. After cooling to room temperature, the solvent was concentrated en vacuo, and the residue was purified by a COMBIFLASH® system (ISCO) using 0-50% ethyl acetate in hexane to give 3-bromo-6-chloro-4-methylpicolinonitrile. After cooling to room temperature the solvent was concentrated en vacuo the residue was purified by a COMBIFLASH® system (ISCO)

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

実験手順: A solution of 5-bromo-2-chloro-4-methylpyridine (1.0 eq.) and meta-chloroperbenzoic acid (mCPBA) (2.5 eq.) in chloroform (0.1 M) was stirred at 50° C. overnight. After cooling to room temperature, Ca(OH)2 (2.5 eq.) was added to the reaction mixture. The precipitate was filtered and washed with 5% methanol in dichloromethane and ethyl acetate. The filtrate was washed with saturated aqueous Na2S2O3 solution and saturated aqueous NaHCO3 solution. The combined organic layers were washed with brine, dried over anhydrous MgSO4, and concentrated en vacuo into a pale solid that was carried onto the next step without further purification. The precipitate was filtered washed with 5% methanol in dichloromethane and ethyl acetate The filtrate was washed with saturated aqueous Na2S2O3 solution and saturated aqueous NaHCO3 solution The combined organic layers were washed with brine dried over anhydrous MgSO4 concentrated en vacuo into a pale solid that was carried onto the next step without further purification

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

実験手順: A solution of 5-bromo-2-chloro-4-methylpyridine (1.0 eq.) and meta-chloroperbenzoic acid (mCPBA) (2.5 eq.) in chloroform (0.1 M) was stirred at 50° C. overnight. After cooling to room temperature, Ca(OH)2 (2.5 eq.) was added to the reaction mixture. The precipitate was filtered and washed with 5% methanol in dichloromethane and ethyl acetate. The filtrate was washed with saturated aqueous Na2S2O3 solution and saturated aqueous NaHCO3 solution. The combined organic layers were washed with brine, dried over anhydrous MgSO4, and concentrated en vacuo into a pale solid that was carried onto the next step without further purification. The precipitate was filtered washed with 5% methanol in dichloromethane and ethyl acetate The filtrate was washed with saturated aqueous Na2S2O3 solution and saturated aqueous NaHCO3 solution The combined organic layers were washed with brine dried over anhydrous MgSO4 concentrated en vacuo into a pale solid that was carried onto the next step without further purification

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 5-bromo-2-chloro-4-methylpyridine 1-oxide (from step 1) (1.0 eq.) in acetonitrile (0.2 M) was added TMSCN (4.0 eq.) and triethylamine (3.0 eq.). The reaction was heated at 100° C. overnight. After cooling to room temperature, the solvent was concentrated en vacuo, and the residue was purified by a COMBIFLASH® system (ISCO) using 0-50% ethyl acetate in hexane to give 3-bromo-6-chloro-4-methylpicolinonitrile. After cooling to room temperature the solvent was concentrated en vacuo the residue was purified by a COMBIFLASH® system (ISCO)

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

実験手順: A solution of 5-bromo-2-chloro-4-methylpyridine (1.0 eq.) and meta-chloroperbenzoic acid (mCPBA) (2.5 eq.) in chloroform (0.1 M) was stirred at 50° C. overnight. After cooling to room temperature, Ca(OH)2 (2.5 eq.) was added to the reaction mixture. The precipitate was filtered and washed with 5% methanol in dichloromethane and ethyl acetate. The filtrate was washed with saturated aqueous Na2S2O3 solution and saturated aqueous NaHCO3 solution. The combined organic layers were washed with brine, dried over anhydrous MgSO4, and concentrated en vacuo into a pale solid that was carried onto the next step without further purification. The precipitate was filtered washed with 5% methanol in dichloromethane and ethyl acetate The filtrate was washed with saturated aqueous Na2S2O3 solution and saturated aqueous NaHCO3 solution The combined organic layers were washed with brine dried over anhydrous MgSO4 concentrated en vacuo into a pale solid that was carried onto the next step without further purification

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 5-bromo-2-chloro-4-methylpyridine 1-oxide (from step 1) (1.0 eq.) in acetonitrile (0.2 M) was added TMSCN (4.0 eq.) and triethylamine (3.0 eq.). The reaction was heated at 100° C. overnight. After cooling to room temperature, the solvent was concentrated en vacuo, and the residue was purified by a COMBIFLASH® system (ISCO) using 0-50% ethyl acetate in hexane to give 3-bromo-6-chloro-4-methylpicolinonitrile. After cooling to room temperature the solvent was concentrated en vacuo the residue was purified by a COMBIFLASH® system (ISCO)

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

実験手順: A solution of 5-bromo-2-chloro-4-methylpyridine (1.0 eq.) and meta-chloroperbenzoic acid (mCPBA) (2.5 eq.) in chloroform (0.1 M) was stirred at 50° C. overnight. After cooling to room temperature, Ca(OH)2 (2.5 eq.) was added to the reaction mixture. The precipitate was filtered and washed with 5% methanol in dichloromethane and ethyl acetate. The filtrate was washed with saturated aqueous Na2S2O3 solution and saturated aqueous NaHCO3 solution. The combined organic layers were washed with brine, dried over anhydrous MgSO4, and concentrated en vacuo into a pale solid that was carried onto the next step without further purification. The precipitate was filtered washed with 5% methanol in dichloromethane and ethyl acetate The filtrate was washed with saturated aqueous Na2S2O3 solution and saturated aqueous NaHCO3 solution The combined organic layers were washed with brine dried over anhydrous MgSO4 concentrated en vacuo into a pale solid that was carried onto the next step without further purification

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 5-bromo-2-chloro-4-methylpyridine 1-oxide (from step 1) (1.0 eq.) in acetonitrile (0.2 M) was added TMSCN (4.0 eq.) and triethylamine (3.0 eq.). The reaction was heated at 100° C. overnight. After cooling to room temperature, the solvent was concentrated en vacuo, and the residue was purified by a COMBIFLASH® system (ISCO) using 0-50% ethyl acetate in hexane to give 3-bromo-6-chloro-4-methylpicolinonitrile. After cooling to room temperature the solvent was concentrated en vacuo the residue was purified by a COMBIFLASH® system (ISCO)

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

実験手順: A solution of 5-bromo-2-chloro-4-methylpyridine (1.0 eq.) and meta-chloroperbenzoic acid (mCPBA) (2.5 eq.) in chloroform (0.1 M) was stirred at 50° C. overnight. After cooling to room temperature, Ca(OH)2 (2.5 eq.) was added to the reaction mixture. The precipitate was filtered and washed with 5% methanol in dichloromethane and ethyl acetate. The filtrate was washed with saturated aqueous Na2S2O3 solution and saturated aqueous NaHCO3 solution. The combined organic layers were washed with brine, dried over anhydrous MgSO4, and concentrated en vacuo into a pale solid that was carried onto the next step without further purification. The precipitate was filtered washed with 5% methanol in dichloromethane and ethyl acetate The filtrate was washed with saturated aqueous Na2S2O3 solution and saturated aqueous NaHCO3 solution The combined organic layers were washed with brine dried over anhydrous MgSO4 concentrated en vacuo into a pale solid that was carried onto the next step without further purification