4-methoxy-2,3,5-trimethyl-1-oxidopyridin-1-ium

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: 215 ml of acetic anhydride were added dropwise at room temperature to a solution of 81.5 g of 4-methoxy-2,3,5-trimethylpyridine 1-oxide in 290 ml of chloroform. After boiling under reflux for 4 hours the solution was evaporated, the residue was dissolved in 200 ml of toluene and again evaporated. The residue was taken up in 500 ml of ethyl acetate and extracted three times with 250 ml of saturated sodium bicarbonate solution. The organic phase was dried over sodium sulfate and evaporated in vacuo. The product which remains behind as the residue was chromatographed on 400 g of silica gel with ether. There was obtained (4-methoxy-3,5-dimethyl-2-pyridyl)methyl acetate in the form of an oil. under reflux for 4 hours the solution was evaporated the residue was dissolved in 200 ml of toluene again evaporated extracted three times with 250 ml of saturated sodium bicarbonate solution The organic phase was dried over sodium sulfate evaporated in vacuo was chromatographed on 400 g of silica gel with ether

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

Procedure: 22.6 g of sodium were dissolved in 4 l of methanol under argon. 120 g of 2,3,5-trimethyl-4-nitropyridine 1-oxide were then added portionwise thereto and the solution was left to boil under reflux overnight. The pH was adjusted to 7 by means of 5N hydrogen chloride in ethyl acetate while cooling and the mixture was then evaporated in vacuo. The residue was taken up in 1.5 l of methylene chloride, the solution was filtered through silica gel, which was rinsed with 0.5 l of methylene chloride, the combined filtrates were evaporated in vacuo and the residue was crystallized from petroleum ether. There was obtained 4-methoxy-2,3,5-trimethylpyridine 1-oxide of melting point 48°-50°. the solution was left under reflux overnight while cooling the mixture was then evaporated in vacuo the solution was filtered through silica gel, which was rinsed with 0.5 l of methylene chloride the combined filtrates were evaporated in vacuo the residue was crystallized from petroleum ether

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

Procedure: 22.6 g of sodium were dissolved in 4 l of methanol under argon. 120 g of 2,3,5-trimethyl-4-nitropyridine 1-oxide were then added portionwise thereto and the solution was left to boil under reflux overnight. The pH was adjusted to 7 by means of 5N hydrogen chloride in ethyl acetate while cooling and the mixture was then evaporated in vacuo. The residue was taken up in 1.5 l of methylene chloride, the solution was filtered through silica gel, which was rinsed with 0.5 l of methylene chloride, the combined filtrates were evaporated in vacuo and the residue was crystallized from petroleum ether. There was obtained 4-methoxy-2,3,5-trimethylpyridine 1-oxide of melting point 48°-50°. the solution was left under reflux overnight while cooling the mixture was then evaporated in vacuo the solution was filtered through silica gel, which was rinsed with 0.5 l of methylene chloride the combined filtrates were evaporated in vacuo the residue was crystallized from petroleum ether

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

Procedure: 215 ml of acetic anhydride were added dropwise at room temperature to a solution of 81.5 g of 4-methoxy-2,3,5-trimethylpyridine 1-oxide in 290 ml of chloroform. After boiling under reflux for 4 hours the solution was evaporated, the residue was dissolved in 200 ml of toluene and again evaporated. The residue was taken up in 500 ml of ethyl acetate and extracted three times with 250 ml of saturated sodium bicarbonate solution. The organic phase was dried over sodium sulfate and evaporated in vacuo. The product which remains behind as the residue was chromatographed on 400 g of silica gel with ether. There was obtained (4-methoxy-3,5-dimethyl-2-pyridyl)methyl acetate in the form of an oil. under reflux for 4 hours the solution was evaporated the residue was dissolved in 200 ml of toluene again evaporated extracted three times with 250 ml of saturated sodium bicarbonate solution The organic phase was dried over sodium sulfate evaporated in vacuo was chromatographed on 400 g of silica gel with ether

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

Procedure: 215 ml of acetic anhydride were added dropwise at room temperature to a solution of 81.5 g of 4-methoxy-2,3,5-trimethylpyridine 1-oxide in 290 ml of chloroform. After boiling under reflux for 4 hours the solution was evaporated, the residue was dissolved in 200 ml of toluene and again evaporated. The residue was taken up in 500 ml of ethyl acetate and extracted three times with 250 ml of saturated sodium bicarbonate solution. The organic phase was dried over sodium sulfate and evaporated in vacuo. The product which remains behind as the residue was chromatographed on 400 g of silica gel with ether. There was obtained (4-methoxy-3,5-dimethyl-2-pyridyl)methyl acetate in the form of an oil. under reflux for 4 hours the solution was evaporated the residue was dissolved in 200 ml of toluene again evaporated extracted three times with 250 ml of saturated sodium bicarbonate solution The organic phase was dried over sodium sulfate evaporated in vacuo was chromatographed on 400 g of silica gel with ether

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

Procedure: 22.6 g of sodium were dissolved in 4 1 of methanol under argon. 120 g of 2,3,5-trimethyl-4-nitropyridine 1-oxide were then added portionwise thereto and the solution was left to boil under reflux overnight. The pH was adjusted to 7 by means of 5N hydrogen chloride in ethyl acetate while cooling and the mixture was then evaporated in vacuo. The residue was taken up in 1.5 1 of methylene chloride, the solution was filtered through silica gel, which was rinsed with 0.5 1 of methylene chloride, the combined filtrates were evaporated in vacuo and the residue was crystallized from petroleum ether. There was obtained 4-methoxy-2,3,5-trimethylpyridine 1-oxide of melting point 48-50° . the solution was left under reflux overnight while cooling the mixture was then evaporated in vacuo the solution was filtered through silica gel, which was rinsed with 0.5 1 of methylene chloride the combined filtrates were evaporated in vacuo the residue was crystallized from petroleum ether

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

Procedure: 30% aqueous sodium hydroxide was added over a solution of crude 2-acetoxymethyl-3,5-dimethyl-4-methoxypyridine prepared from 30.06 g (0.18 mole) of 2,3,5-trimethyl-4-methoxypyridine N-oxide, to pH 13. The mass was stirred for about 3.5 hours at 25°-28° C., with addition of 30% aqueous sodium hydroxide at the appropriate rate to hold the pH to between 11.7 and 13. Once the reaction was terminated (complete disappearance of the band located towards 1700 cm-1) the pH was adjusted to 6.5 with acetic acid, water was added and the mass was extracted with methylene chloride. The solvent was removed by vacuum distillation and finally 2-hydroxymethyl-3,5-dimethyl-4-methoxypyridine was distilled at 142°-145° C. (9 torr.) as a colourless liquid which crystallised on standing. 27.23 g were obtained. Yield 92.4%. Once the reaction was terminated (complete disappearance of the band was added the mass was extracted with methylene chloride The solvent was removed by vacuum distillation and finally 2-hydroxymethyl-3,5-dimethyl-4-methoxypyridine was distilled at 142°-145° C. (9 torr.) as a colourless liquid which crystallised 27.23 g were obtained

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

Procedure: A solution of 30.06 g (0.18 mole) of 2,3,5-trimethyl-4-methoxypyridine N-oxide in 100 ml of methylene chloride was added slowly (over approximately one hour) over a solution of 0.38 g of dimethylaminopyridine in 53.4 ml (0.565 mole) of acetic anhydride, heated to 90°-95° C., with the temperature being held within the abovementioned range and the methylene chloride being removed by distillation. At the end of the addition, the distillation was continued for a further 10 minutes, the mixture was cooled to below 90° C. and 7.5 ml of water were added slowly, holding the temperature below 90° C. Crude 2-acetoxymethyl-3,5-dimethyl-4-methoxypyridine was obtained by distillation at reduced pressure and was used directly as starting product for the hydrolysis (Example 2). heated to 90°-95° C., with the temperature the methylene chloride being removed by distillation At the end of the addition the distillation the mixture was cooled to below 90° C. 7.5 ml of water were added slowly the temperature below 90° C