2,6-Dimethylpyridine N-oxide

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

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

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

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: The 4-nitro substituted starting material is prepared by contacting 2,6-dimethylpyridine N-oxide with nitric acid and sulfuric acid thereby forming the 2,6-dimethyl-4-nitropyridine. The N-oxide is reduced to the pyridine compound with phosphorous trichloride and then oxidized to the 4-nitropyridine 2,6-dicarboxylic acid with potassium permanganate. is prepared

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

Procedure: The 4-nitro substituted starting material is prepared by contacting 2,6-dimethylpyridine N-oxide with nitric acid and sulfuric acid thereby forming the 2,6-dimethyl-4-nitropyridine. The N-oxide is reduced to the pyridine compound with phosphorous trichloride and then oxidized to the 4-nitropyridine 2,6-dicarboxylic acid with potassium permanganate. is prepared

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

Procedure: To a stirred solution of 5.0 g (44.6 mmol) of cyclohexanecarboxaldehyde in n-butyl acetate (45 mL) cooled in a wet-ice bath (ca. 2° C.) was added 5.5 g (44.6 mmol) of 2,6-dimethylpyridine N-oxide (2,6-lutidine N-oxide). To this solution was then added slowly dropwise 24.6 mL (66.9 mmol) of a 23.0 weight percent solution of peracetic acid in ethyl acetate, at a rate slow enough such that the reaction temperature did not exceed 10° C. (ca. 20 min). After the initial exotherm, the temperature returned to 2° C., and the reaction was maintained at this temperature for an additional 4 hours. The cold reaction solution Was then transferred into a separatory funnel, was diluted with n-butyl acetate (50 mL), and was washed with a 1% aqueous solution of sodium thiosulfate (Na2S2O3, 50 mL). The butyl acetate layer was further washed with two portions of water (50 mL each), and the combined water washes were back-extracted with n-butyl acetate (50 ml). The combined butyl acetate layers were extracted with two portions of a 5% aqueous solution of sodium hydroxide (NaOH, 50 mL each). The combined NaOH solutions were acidified to pH=1 with a 10% aqueous solution of hydrochloric acid. The resulting solution was extracted with two portions of dichloromethane (75 mL each), and the extract was dried over anhydrous Na2SO4. The extract was filtered and concentrated in vacuo to give 6.0 g (99%) of cyclohexanecarboxylic acid, containing small levels of unidentified impurities. did not exceed 10° C. (ca. 20 min) returned to 2° C. the reaction was maintained at this temperature for an additional 4 hours The cold reaction solution Was then transferred into a separatory funnel was washed with a 1% aqueous solution of sodium thiosulfate (Na2S2O3, 50 mL) The butyl acetate layer was further washed with two portions of water (50 mL each) the combined water washes were back-extracted with n-butyl acetate (50 ml) The combined butyl acetate layers were extracted with two portions of a 5% aqueous solution of sodium hydroxide (NaOH, 50 mL each) The resulting solution was extracted with two portions of dichloromethane (75 mL each) the extract was dried over anhydrous Na2SO4 The extract was filtered concentrated in vacuo

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

Procedure: A solution of 2,6-lutidine N-oxide (41.6 g, 0.337 mol, 1.0 equiv.) in dry DCM (650 mL) was added to a flask containing trimethyloxonium tetrafluoroborate (50.0 g, 0.337 mol, 1.0 equiv.) at room temperature. under a nitrogen atmosphere. The mixture was stirred at room temperature for 3.0 hours, then concentrated in vacuo to give 78 g of crude 4-hydroxymethyl-2,6-dimethylpyridine. The crude product was dissolved in methanol (500 mL) and the solution was heated to reflux under a nitrogen atmosphere, then a solution of ammonium persulfate (24.6 g, 0.101 mol) in water (100 mL) was added dropwise. The mixture was stirred at reflux for 16 hours; TLC indicated complete reaction. Half of the solvents were removed in vacuo, then quenched with 10% NaOH solution to pH approximately 7, and evaporated to dryness. The residue was dissolved in methanol and filtered, the filtrate was concentrated in vacuum, and purified by column chromatography (eluting with methanol: DCM=5-15%) to give the title compound as a white solid. Yield: 24.7 g (52%). concentrated in vacuo

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

Procedure: A solution of 2,6-lutidine N-oxide (41.6 g, 0.337 mol, 1.0 equiv.) in dry DCM (650 mL) was added to a flask containing trimethyloxonium tetrafluoroborate (50.0 g, 0.337 mol, 1.0 equiv.) at room temperature. under a nitrogen atmosphere. The mixture was stirred at room temperature for 3.0 hours, then concentrated in vacuo to give 78 g of crude 4-hydroxymethyl-2,6-dimethylpyridine. The crude product was dissolved in methanol (500 mL) and the solution was heated to reflux under a nitrogen atmosphere, then a solution of ammonium persulfate (24.6 g, 0.101 mol) in water (100 mL) was added dropwise. The mixture was stirred at reflux for 16 hours; TLC indicated complete reaction. Half of the solvents were removed in vacuo, then quenched with 10% NaOH solution to pH approximately 7, and evaporated to dryness. The residue was dissolved in methanol and filtered, the filtrate was concentrated in vacuum, and purified by column chromatography (eluting with methanol: DCM=5-15%) to give the title compound as a white solid. Yield: 24.7 g (52%). concentrated in vacuo

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

Procedure: A solution of 2,6-lutidine N-oxide (24.0 g, 0.20 mol) in anhydrous dichloromethane (400 mL) was added to trimethyloxonium tetrafluoroborate (29.6 g, 0.20 mol) at room temperature under nitrogen atmosphere and the reaction mixture was stirred at room temperature for 3 hours. The mixture was concentrated in vacuo to give the crude product, 1-methoxy-2,6-dimethyl-pyridinium tetrafluoroborate. The mixture was concentrated in vacuo

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

Procedure: A solution of 2,6-dimethylpyridine 1-oxide (980 mg, 0.79 mmol) in acetic anhydride (5 mL) was refluxed for 1 h. The reaction mixture was then concentrated in vacuo to obtain the crude product. The crude material was purified via silica gel column chromatography using 20% ethyl acetate in hexanes to afford (6-methylpyridin-2-yl)methyl acetate (1.0 g) as a solid. The reaction mixture was then concentrated in vacuo to obtain the crude product The crude material was purified via silica gel column chromatography