2-chloro-6-methyl-1-oxidopyridin-1-ium

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: 2-Chloro-6-methyl-pyridine 1-oxide (5.0 g, 0.035 mol) was dissolved in concentrated sulfuric acid (20 ml) at 0° C. An ice-cooled mixture of concentrated nitric acid (12 ml) in concentrated sulfuric acid (20 ml) was added dropwise with stirring at 0° C. The cooling bath was removed, stirring was continued for 3 hours at 90° C. The mixture was poured into a mixture of icewater and ethyl acetate and the resulting precipitate was removed by filtration. The phases of the filtrate were separated, the aqueous phase was extracted several times with ethyl acetate, basified with NaOH and extracted again with ethyl acetate. The combined organic phases were dried over magnesium sulfate and the solvent removed under reduced pressure. The residue was combined with the filtered residue above to yield 6.21 g of a yellow solid (0.033 mol, 94%). MS (ESI) m/z=189.0 [M+1]+. was added dropwise The cooling bath was removed stirring The mixture was poured into a mixture of icewater and ethyl acetate the resulting precipitate was removed by filtration The phases of the filtrate were separated the aqueous phase was extracted several times with ethyl acetate extracted again with ethyl acetate The combined organic phases were dried over magnesium sulfate the solvent removed under reduced pressure

Conditions: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Chloro-6-methylpyridine (12.76 g, 0.1 mol) was dissolved together with m-chloroperbenzoic acid (17.56 g, 0.15 mol) in DCM (100 ml) and stirred at 40° C. for 90 minutes. The heating bath was removed and stirring was continued overnight at room temperature. The reaction mixture was quenched with saturated sodium thiosulfate solution and the pH was adjusted to 8 with 1M NaOH. The phases were separated, the aqueous phase extracted with DCM and the combined organic phases were dried over magnesium sulfate. The solvent was removed under reduced pressure and unreacted 2-chloro-6-methylpyridine was removed by distillation (2 mbar, 65° C.). 2-Chloro-6-methyl-pyridine 1-oxide was obtained as residue (6.0 g of a yellow oil, 0.042 mol, 42%). MS (ESI) m/z=144.0 [M+1]+. The heating bath was removed stirring was continued overnight at room temperature The reaction mixture was quenched with saturated sodium thiosulfate solution The phases were separated the aqueous phase extracted with DCM the combined organic phases were dried over magnesium sulfate The solvent was removed under reduced pressure and unreacted 2-chloro-6-methylpyridine was removed by distillation (2 mbar, 65° C.)

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

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

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

Procedure: To a slurry of sodium hydride (4.2 g, 105 mmol; 60% dispersion in mineral oil) in anhydrous dimethyl sulfoxide (70 mL), benzyl alcohol (8.7 mL, 84 mmol) was added over a period of 10 minute. The mixture was stirred at room temp. for 10 h., and treated with a solution of 2-chloro-6-methylpyridine N-oxide (10 g, 70 mmol) in dimethyl sulfoxide (10 mL). The resultant mixture was stirred at room temp. overnight, quenched with water and aqueous hydrochloric acid (to pH 8). The mixture was extracted with chloroform. The organic extract was dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The residue was subjected to column chromatography on silica gel eluting with 1-4% methanol in chloroform gradient. Collection and concentration of appropriate fractions provided 2-benzyloxy-6-methylpyridine N-oxide as pale brown oil. quenched with water and aqueous hydrochloric acid (to pH 8) The mixture was extracted with chloroform The organic extract was dried over anhydrous sodium sulfate filtered concentrated under vacuum Collection and concentration of appropriate fractions

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

Procedure: To a cold (0° C.) solution of 2-chloro-6-methylpyridine (24.6 g, 193 mmol) in dichloromethane (100 mL), a solution of m-chloro-per-benzoic acid (46.2 g, 268 mmol; purified) in dichloromethane (480 mL) was added over a period of 30 min. The reaction mixture was stirred at room temp. overnight, and concentrated to about 100 mL. The slurry was filtered, and the solid washed with ice-cold dichloromethane. The combined filtrate was washed with saturated aqueous sodium bicarbonate, brine, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under vacuum to provide 2-chloro-6-methylpyridine N-oxide as clear colorless oil. concentrated to about 100 mL The slurry was filtered the solid washed with ice-cold dichloromethane The combined filtrate was washed with saturated aqueous sodium bicarbonate, brine dried over anhydrous magnesium sulfate filtered The filtrate was concentrated under vacuum

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

Procedure: To a cold (0° C.) solution of 2-chloro-6-methylpyridine (24.6 g, 193 mmol) in dichloromethane (100 mL), a solution of m-chloro-per-benzoic acid (46.2 g, 268 mmol; purified) in dichloromethane (480 mL) was added over a period of 30 min. The reaction mixture was stirred at room temp. overnight, and concentrated to about 100 mL. The slurry was filtered, and the solid washed with ice-cold dichloromethane. The combined filtrate was washed with saturated aqueous sodium bicarbonate, brine, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under vacuum to provide 2-chloro-6-methylpyridine N-oxide as clear colorless oil. concentrated to about 100 mL The slurry was filtered the solid washed with ice-cold dichloromethane The combined filtrate was washed with saturated aqueous sodium bicarbonate, brine dried over anhydrous magnesium sulfate filtered The filtrate was concentrated under vacuum

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

Procedure: To a slurry of sodium hydride (4.2 g, 105 mmol; 60% dispersion in mineral oil) in anhydrous dimethyl sulfoxide (70 mL), benzyl alcohol (8.7 mL, 84 mmol) was added over a period of 10 minute. The mixture was stirred at room temp. for 10 h., and treated with a solution of 2-chloro-6-methylpyridine N-oxide (10 g, 70 mmol) in dimethyl sulfoxide (10 mL). The resultant mixture was stirred at room temp. overnight, quenched with water and aqueous hydrochloric acid (to pH 8). The mixture was extracted with chloroform. The organic extract was dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The residue was subjected to column chromatography on silica gel eluting with 1-4% methanol in chloroform gradient. Collection and concentration of appropriate fractions provided 2-benzyloxy-6-methylpyridine N-oxide as pale brown oil. quenched with water and aqueous hydrochloric acid (to pH 8) The mixture was extracted with chloroform The organic extract was dried over anhydrous sodium sulfate filtered concentrated under vacuum Collection and concentration of appropriate fractions

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

Procedure: To a cold (0° C.) solution of 2-chloro-6-methylpyridine (24.6 g, 193 mmol) in dichloromethane (100 mL), a solution of m-chloro-per-benzoic acid (46.2 g, 268 mmol; purified) in dichloromethane (480 mL) was added over a period of 30 min. The reaction mixture was stirred at room temp. overnight, and concentrated to about 100 mL. The slurry was filtered, and the solid washed with ice-cold dichloromethane. The combined filtrate was washed with saturated aqueous sodium bicarbonate, brine, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under vacuum to provide 2-chloro-6-methylpyridine N-oxide as clear colorless oil. concentrated to about 100 mL The slurry was filtered the solid washed with ice-cold dichloromethane The combined filtrate was washed with saturated aqueous sodium bicarbonate, brine dried over anhydrous magnesium sulfate filtered The filtrate was concentrated under vacuum

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

Procedure: 2-Chloro-6-methyl-pyridine 1-oxide (5.0 g, 0.035 mol) was dissolved in concentrated sulfuric acid (20 ml) at 0° C. An ice-cooled mixture of concentrated nitric acid (12 ml) in concentrated sulfuric acid (20 ml) was added dropwise with stirring at 0° C. The cooling bath was removed, stirring was continued for 3 hours at 90° C. The mixture was poured into a mixture of icewater and ethyl acetate and the resulting precipitate was removed by filtration. The phases of the filtrate were separated, the aqueous phase was extracted several times with ethyl acetate, basified with NaOH and extracted again with ethyl acetate. The combined organic phases were dried over magnesium sulfate and the solvent removed under reduced pressure. The residue was combined with the filtered residue above to yield 6.21 g of a yellow solid (0.033 mol, 94%). MS (ESI) m/z=189.0 [M+1]+. was added dropwise The cooling bath was removed stirring The mixture was poured into a mixture of icewater and ethyl acetate the resulting precipitate was removed by filtration The phases of the filtrate were separated the aqueous phase was extracted several times with ethyl acetate extracted again with ethyl acetate The combined organic phases were dried over magnesium sulfate the solvent removed under reduced pressure