4-Methoxy-3,5-diMethylpyridine 1-Oxide

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

実験手順: 3.5-Dimethyl-4-methoxypyridine-N-oxide (61.2 g) obtained in Example 2 was dissolved in CH3OH (458 ml). Dimethylsulfate (38 ml 0.4 moles) was added dropwise during 15 minutes and pH adjusted to 5.0 using 10M NaOH. The mixture was stirred for 15 minutes and thereafter refluxed for 1 hour. An additional amount of dimethylsulfate (3.8 ml, 0.04 moles) was added dropwise and the mixture was refluxed for 1.5 hours. Stirring was continued overnight at room temperature. Thereafter the mixture was heated to reflux and (NH4)2S2O8 (91.2 g, 0.4 moles) dissolved in water (169 ml) was added during 1.75 hours, followed by refluxing for 1.5 hours and stirring at room temperature overnight. Thereafter CH3OH (452 ml) was added. Precipitated salts were filtered off and discarded. After evaporation of CH3OH, the remaining water phase (pH 0.6) was adjusted to pH 10.0 using 10M NaOH (145 ml). The water phase was extracted three times with CH2Cl2. The combined CH2Cl2 phases were dried over Na2SO4, evaporated and dried, yielding 3,5-dimethyl-4-methoxy-2-hydroxymethylpyridine (44.2 g). The identity of the product was confirmed with 1H and 13C NMR and the purity checked with gas chromatography. refluxed for 1 hour the mixture was refluxed for 1.5 hours Stirring was continued overnight at room temperature Thereafter the mixture was heated to reflux was added during 1.75 hours by refluxing for 1.5 hours stirring at room temperature overnight Precipitated salts were filtered off After evaporation of CH3OH The water phase was extracted three times with CH2Cl2 The combined CH2Cl2 phases were dried over Na2SO4 evaporated dried

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

実験手順: 3.5-Dimethyl-4-methoxypyridine-N-oxide (61.2 g) obtained in Example 2 was dissolved in CH3OH (458 ml). Dimethylsulfate (38 ml 0.4 moles) was added dropwise during 15 minutes and pH adjusted to 5.0 using 10M NaOH. The mixture was stirred for 15 minutes and thereafter refluxed for 1 hour. An additional amount of dimethylsulfate (3.8 ml, 0.04 moles) was added dropwise and the mixture was refluxed for 1.5 hours. Stirring was continued overnight at room temperature. Thereafter the mixture was heated to reflux and (NH4)2S2O8 (91.2 g, 0.4 moles) dissolved in water (169 ml) was added during 1.75 hours, followed by refluxing for 1.5 hours and stirring at room temperature overnight. Thereafter CH3OH (452 ml) was added. Precipitated salts were filtered off and discarded. After evaporation of CH3OH, the remaining water phase (pH 0.6) was adjusted to pH 10.0 using 10M NaOH (145 ml). The water phase was extracted three times with CH2Cl2. The combined CH2Cl2 phases were dried over Na2SO4, evaporated and dried, yielding 3,5-dimethyl-4-methoxy-2-hydroxymethylpyridine (44.2 g). The identity of the product was confirmed with 1H and 13C NMR and the purity checked with gas chromatography. refluxed for 1 hour the mixture was refluxed for 1.5 hours Stirring was continued overnight at room temperature Thereafter the mixture was heated to reflux was added during 1.75 hours by refluxing for 1.5 hours stirring at room temperature overnight Precipitated salts were filtered off After evaporation of CH3OH The water phase was extracted three times with CH2Cl2 The combined CH2Cl2 phases were dried over Na2SO4 evaporated dried

反応条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 3,5-lutidine (15 kg, 140.2 moles) was dissolved in acetic acid (48 l) at 60° C. Hydrogen peroxide (8430 ml, 98 moles) was added during 3 hours. The solution was heated to 90° C. and kept at this temperature for 3 hours. The reaction mixture was cooled to 60° C. and hydrogen peroxide (3500 ml, 41 moles) was added during 1 hour. The temperature was raised to 90° C. and kept there for 16 hours. The reaction mixture was evaporated at reduced pressure (70° C. 300 mm Hg). The residue (approx 25 liters) was cooled and pH adjusted to 10 with NaOH-solution (23 liters 10M). Acetonitrile (30 liters) was added and the mixture was stirred for 30 minutes. The sodiumacetate was separated off and washed with 10 l acetonitrile. The liquid phase was evaporated at reduced pressure (55° C., 200 mm Hg). The remaining solution (approx 25 liters) was extracted with CH2Cl2 (20 liters and 3×5 liters). The combined organic layers were dried over MgSO4, filtrated and evaporated at reduced pressure (50° C. 200 mm Hg). When all CH2Cl2 had distilled off unreacted 3,5-lutidine was evaporated at 75° C., 8 mm Hg. Yield 14940 g of 3,5-dimethylpyridine-N-oxide. The identity was confirmed with 1 H and 13C NMR. The reaction mixture was cooled to 60° C. The temperature was raised to 90° C. kept there for 16 hours The reaction mixture was evaporated at reduced pressure (70° C. 300 mm Hg) The residue (approx 25 liters) was cooled Acetonitrile (30 liters) was added The sodiumacetate was separated off washed with 10 l acetonitrile The liquid phase was evaporated at reduced pressure (55° C., 200 mm Hg) The remaining solution (approx 25 liters) was extracted with CH2Cl2 (20 liters and 3×5 liters) The combined organic layers were dried over MgSO4 filtrated evaporated at reduced pressure (50° C. 200 mm Hg) When all CH2Cl2 had distilled off unreacted 3,5-lutidine was evaporated at 75° C.

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

実験手順: 3.5-Dimethyl-4-methoxypyridine-N-oxide (61.2 g) obtained in Example 2 was dissolved in CH3OH (458 ml). Dimethylsulfate (38 ml 0.4 moles) was added dropwise during 15 minutes and pH adjusted to 5.0 using 10M NaOH. The mixture was stirred for 15 minutes and thereafter refluxed for 1 hour. An additional amount of dimethylsulfate (3.8 ml, 0.04 moles) was added dropwise and the mixture was refluxed for 1.5 hours. Stirring was continued overnight at room temperature. Thereafter the mixture was heated to reflux and (NH4)2S2O8 (91.2 g, 0.4 moles) dissolved in water (169 ml) was added during 1.75 hours, followed by refluxing for 1.5 hours and stirring at room temperature overnight. Thereafter CH3OH (452 ml) was added. Precipitated salts were filtered off and discarded. After evaporation of CH3OH, the remaining water phase (pH 0.6) was adjusted to pH 10.0 using 10M NaOH (145 ml). The water phase was extracted three times with CH2Cl2. The combined CH2Cl2 phases were dried over Na2SO4, evaporated and dried, yielding 3,5-dimethyl-4-methoxy-2-hydroxymethylpyridine (44.2 g). The identity of the product was confirmed with 1H and 13C NMR and the purity checked with gas chromatography. refluxed for 1 hour the mixture was refluxed for 1.5 hours Stirring was continued overnight at room temperature Thereafter the mixture was heated to reflux was added during 1.75 hours by refluxing for 1.5 hours stirring at room temperature overnight Precipitated salts were filtered off After evaporation of CH3OH The water phase was extracted three times with CH2Cl2 The combined CH2Cl2 phases were dried over Na2SO4 evaporated dried

反応条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 3,5-lutidine (15 kg, 140.2 moles) was dissolved in acetic acid (48 l) at 60° C. Hydrogen peroxide (8430 ml, 98 moles) was added during 3 hours. The solution was heated to 90° C. and kept at this temperature for 3 hours. The reaction mixture was cooled to 60° C. and hydrogen peroxide (3500 ml, 41 moles) was added during 1 hour. The temperature was raised to 90° C. and kept there for 16 hours. The reaction mixture was evaporated at reduced pressure (70° C. 300 mm Hg). The residue (approx 25 liters) was cooled and pH adjusted to 10 with NaOH-solution (23 liters 10M). Acetonitrile (30 liters) was added and the mixture was stirred for 30 minutes. The sodiumacetate was separated off and washed with 10 l acetonitrile. The liquid phase was evaporated at reduced pressure (55° C., 200 mm Hg). The remaining solution (approx 25 liters) was extracted with CH2Cl2 (20 liters and 3×5 liters). The combined organic layers were dried over MgSO4, filtrated and evaporated at reduced pressure (50° C. 200 mm Hg). When all CH2Cl2 had distilled off unreacted 3,5-lutidine was evaporated at 75° C., 8 mm Hg. Yield 14940 g of 3,5-dimethylpyridine-N-oxide. The identity was confirmed with 1 H and 13C NMR. The reaction mixture was cooled to 60° C. The temperature was raised to 90° C. kept there for 16 hours The reaction mixture was evaporated at reduced pressure (70° C. 300 mm Hg) The residue (approx 25 liters) was cooled Acetonitrile (30 liters) was added The sodiumacetate was separated off washed with 10 l acetonitrile The liquid phase was evaporated at reduced pressure (55° C., 200 mm Hg) The remaining solution (approx 25 liters) was extracted with CH2Cl2 (20 liters and 3×5 liters) The combined organic layers were dried over MgSO4 filtrated evaporated at reduced pressure (50° C. 200 mm Hg) When all CH2Cl2 had distilled off unreacted 3,5-lutidine was evaporated at 75° C.

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

実験手順: 3.5-Dimethyl-4-methoxypyridine-N-oxide (61.2 g) obtained in Example 2 was dissolved in CH3OH (458 ml). Dimethylsulfate (38 ml 0.4 moles) was added dropwise during 15 minutes and pH adjusted to 5.0 using 10M NaOH. The mixture was stirred for 15 minutes and thereafter refluxed for 1 hour. An additional amount of dimethylsulfate (3.8 ml, 0.04 moles) was added dropwise and the mixture was refluxed for 1.5 hours. Stirring was continued overnight at room temperature. Thereafter the mixture was heated to reflux and (NH4)2S2O8 (91.2 g, 0.4 moles) dissolved in water (169 ml) was added during 1.75 hours, followed by refluxing for 1.5 hours and stirring at room temperature overnight. Thereafter CH3OH (452 ml) was added. Precipitated salts were filtered off and discarded. After evaporation of CH3OH, the remaining water phase (pH 0.6) was adjusted to pH 10.0 using 10M NaOH (145 ml). The water phase was extracted three times with CH2Cl2. The combined CH2Cl2 phases were dried over Na2SO4, evaporated and dried, yielding 3,5-dimethyl-4-methoxy-2-hydroxymethylpyridine (44.2 g). The identity of the product was confirmed with 1H and 13C NMR and the purity checked with gas chromatography. refluxed for 1 hour the mixture was refluxed for 1.5 hours Stirring was continued overnight at room temperature Thereafter the mixture was heated to reflux was added during 1.75 hours by refluxing for 1.5 hours stirring at room temperature overnight Precipitated salts were filtered off After evaporation of CH3OH The water phase was extracted three times with CH2Cl2 The combined CH2Cl2 phases were dried over Na2SO4 evaporated dried

反応条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 3,5-lutidine (15 kg, 140.2 moles) was dissolved in acetic acid (48 l) at 60° C. Hydrogen peroxide (8430 ml, 98 moles) was added during 3 hours. The solution was heated to 90° C. and kept at this temperature for 3 hours. The reaction mixture was cooled to 60° C. and hydrogen peroxide (3500 ml, 41 moles) was added during 1 hour. The temperature was raised to 90° C. and kept there for 16 hours. The reaction mixture was evaporated at reduced pressure (70° C. 300 mm Hg). The residue (approx 25 liters) was cooled and pH adjusted to 10 with NaOH-solution (23 liters 10M). Acetonitrile (30 liters) was added and the mixture was stirred for 30 minutes. The sodiumacetate was separated off and washed with 10 l acetonitrile. The liquid phase was evaporated at reduced pressure (55° C., 200 mm Hg). The remaining solution (approx 25 liters) was extracted with CH2Cl2 (20 liters and 3×5 liters). The combined organic layers were dried over MgSO4, filtrated and evaporated at reduced pressure (50° C. 200 mm Hg). When all CH2Cl2 had distilled off unreacted 3,5-lutidine was evaporated at 75° C., 8 mm Hg. Yield 14940 g of 3,5-dimethylpyridine-N-oxide. The identity was confirmed with 1 H and 13C NMR. The reaction mixture was cooled to 60° C. The temperature was raised to 90° C. kept there for 16 hours The reaction mixture was evaporated at reduced pressure (70° C. 300 mm Hg) The residue (approx 25 liters) was cooled Acetonitrile (30 liters) was added The sodiumacetate was separated off washed with 10 l acetonitrile The liquid phase was evaporated at reduced pressure (55° C., 200 mm Hg) The remaining solution (approx 25 liters) was extracted with CH2Cl2 (20 liters and 3×5 liters) The combined organic layers were dried over MgSO4 filtrated evaporated at reduced pressure (50° C. 200 mm Hg) When all CH2Cl2 had distilled off unreacted 3,5-lutidine was evaporated at 75° C.