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

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

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

Procedure: To a solution of 5-bromo-2-methylpyridine 1-oxide (from step 1) (1.0 eq.) in acetonitrile (0.2 M) was added trimethylsilyl cyanide (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-methylpicolinonitrile. After cooling to room temperature the solvent was concentrated en vacuo the residue was purified by a COMBIFLASH® system (ISCO)

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 5-bromo-2-methylpyridine (1.0 eq.) in chloroform (0.38 M) was added 77% meta-chloroperbenzoic acid (mCPBA) (4.0 eq.) and heated at 60° C. for 20 hours. After cooling to room temperature, Ca(OH)2 (5.3 eq.) was added, and the resulting precipitate was stirred for 30 minutes. The precipitate was filtered and washed with 3:1 CHCl3/methanol. The filtrate was concentrated en vacuo to give a solid, which was stirred in 30% ethyl acetate in hexane and filtered to give the desired N-oxide. The filtrate was concentrated en vacuo, and the residue was purified by a COMBIFLASH® system (ISCO) using 0-100% ethyl acetate in hexane to give more of the desired N-oxide. The two batches were combined and carried onto the next step. After cooling to room temperature The precipitate was filtered washed with 3:1 CHCl3/methanol The filtrate was concentrated en vacuo to give a solid, which filtered

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

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 5-Bromo-2-methylpyridine 1-oxide (5.36 g) was added to a mixture of conc. nitric acid (10.1 mL) and conc. sulfuric acid (8.94 mL), and the mixture was stirred at 90° C. for 20 hr. The reaction mixture was poured into ice water, and the resulting pale-yellow precipitate was collected by filtration. The crude crystals were washed with water to give the title compound (3.83 g) as a pale-yellow solid. The filtrate was neutralized with 8N aqueous sodium hydroxide solution at room temperature, and extracted with a mixed solvent of ethyl acetate and THF. The extract was washed with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (NH, ethyl acetate/hexane) to give the title compound (360 mg) as a pale-yellow solid. the resulting pale-yellow precipitate was collected by filtration The crude crystals were washed with water

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

Procedure: To a solution of 5-bromo-2-methylpyridine (5.00 g) in acetonitrile (30 mL) was added 70% m-chloroperbenzoic acid (10.8 g), and the mixture was stirred at room temperature for 30 min. The resulting white precipitate was filtered off, and the solvent in the filtrate was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (NH, methanol/ethyl acetate) and recrystallized (ethyl acetate/hexane) to give the title compound (5.36 g) as a pale-yellow solid. The resulting white precipitate was filtered off the solvent in the filtrate was evaporated under reduced pressure The residue was purified by silica gel column chromatography (NH, methanol/ethyl acetate) recrystallized (ethyl acetate/hexane)

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

Procedure: To a solution of 5-bromo-2-methylpyridine (5.00 g) in acetonitrile (30 mL) was added 70% m-chloroperbenzoic acid (10.8 g), and the mixture was stirred at room temperature for 30 min. The resulting white precipitate was filtered off, and the solvent in the filtrate was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (NH, methanol/ethyl acetate) and recrystallized (ethyl acetate/hexane) to give the title compound (5.36 g) as a pale-yellow solid. The resulting white precipitate was filtered off the solvent in the filtrate was evaporated under reduced pressure The residue was purified by silica gel column chromatography (NH, methanol/ethyl acetate) recrystallized (ethyl acetate/hexane)

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

Procedure: To a solution of 5-bromo-2-methylpyridine 1-oxide (from step 1) (1.0 eq.) in acetonitrile (0.2 M) was added trimethylsilyl cyanide (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-methylpicolinonitrile. After cooling to room temperature the solvent was concentrated en vacuo the residue was purified by a COMBIFLASH® system (ISCO)

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

Procedure: To a solution of 5-bromo-2-methylpyridine 1-oxide (from step 1) (1.0 eq.) in acetonitrile (0.2 M) was added trimethylsilyl cyanide (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-methylpicolinonitrile. After cooling to room temperature the solvent was concentrated en vacuo the residue was purified by a COMBIFLASH® system (ISCO)

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 5-bromo-2-methylpyridine (1.0 eq.) in chloroform (0.38 M) was added 77% meta-chloroperbenzoic acid (mCPBA) (4.0 eq.) and heated at 60° C. for 20 hours. After cooling to room temperature, Ca(OH)2 (5.3 eq.) was added, and the resulting precipitate was stirred for 30 minutes. The precipitate was filtered and washed with 3:1 CHCl3/methanol. The filtrate was concentrated en vacuo to give a solid, which was stirred in 30% ethyl acetate in hexane and filtered to give the desired N-oxide. The filtrate was concentrated en vacuo, and the residue was purified by a COMBIFLASH® system (ISCO) using 0-100% ethyl acetate in hexane to give more of the desired N-oxide. The two batches were combined and carried onto the next step. After cooling to room temperature The precipitate was filtered washed with 3:1 CHCl3/methanol The filtrate was concentrated en vacuo to give a solid, which filtered

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

Procedure: To the solution of 5-bromo-2-methylpyridine 1-oxide (8.935 g, 47.52 mmol) in acetonitrile (240 mL) was added trimethylsilyl cyanide (TMSCN) (25 mL, 190 mmol) and triethylamine (20 mL, 142.56 mmol). The reaction was heated at 100° C. for 16 h. The mixture was cooled to rt and concentrated in vacuo. The crude was purified by silica gel chromatography using 0-50% EtOAc in hexane to obtain the title compound. The mixture was cooled to rt concentrated in vacuo The crude was purified by silica gel chromatography

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

Procedure: A solution of 5-bromo-2-methylpyridine (10 g, 58.13 mmol) and meta-chloroperbenzoic acid (mCPBA, 30 g, 174.39 mmol) in CHCl3 (160 mL) was heated at 60° C. for 16 h. The mixture was cooled to rt and neutralized with satd. NaHCO3. The resulting mixture was extracted with DCM. The organic layers were combined and washed with brine and dried (MgSO4). The solvent was removed in vacuo. The crude was purified by silica gel chromatography (EtOAc/hexanes) to obtain the title compound. The resulting mixture was extracted with DCM washed with brine dried (MgSO4) The solvent was removed in vacuo The crude was purified by silica gel chromatography (EtOAc/hexanes)