4-tert-butyl-1-oxidopyridin-1-ium

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To stirred dimethyl sulfate (6.70 g) was added slowly 4-tert-butyl-1-oxypyridine (8.0 g) at ca. 10° C. in an ice-water bath and the mixture was stirred for 3 hours at 80° C. After cooling to room temperature, to the mixture was added a mixture of ethanol and water (1:1, 60 ml) under stirring. To the mixture was added dropwise an aqueous solution of potassium cyanate (6.9 g in 20 ml of water) below 10° C. and stirring for 1 hour under the same condition, and then overnight at room temperature. To the resultant mixture was added 150 ml of water and the resultant mixture was extracted with CHCl3. The organic layer was dried over sodium sulfate, filtered and concentrated in vacuo. A crude compound was purified by column chromatography on silica gel with a mixture of ethyl acetate and n-hexane to give 4-tert-butyl-2-cyanopyridine (4.6 g) as a yellow oil. After cooling to room temperature, to the mixture was added under stirring stirring for 1 hour under the same condition overnight at room temperature the resultant mixture was extracted with CHCl3 The organic layer was dried over sodium sulfate filtered concentrated in vacuo A crude compound was purified by column chromatography on silica gel with a mixture of ethyl acetate and n-hexane

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

実験手順: To a stirred solution of 4-tert-butylpyridine (19.0 g) in acetic acid (90 ml) was added dropwise 50% of hydrogen peroxide aqueous solution (20 ml) at room temperature and stirred for 30 minutes under the same condition. The mixture was stirred for 3 hours at ca.80° C. After cooling to room temperature, to the mixture was added dropwise another 20 ml of 50% hydrogen peroxide aqueous solution and stirred for 30 minutes. The mixture was stirred for 3 hours at ca. 80° C. After cooling to room temperature, the mixture was concentrated in vacuo. The residue was taken up with chloroform, and washed with water (50 ml), saturated sodium carbonate aqueous solution (50 ml) and water (50 ml). The organic layer was dried over sodium sulfate, filtered and concentrated in vacuo to give 4-tert-butyl-1-oxypyridine, which was crystallized by isopropyl ether as a colorless powder (19.1 g). The mixture was stirred for 3 hours at ca 80° C stirred for 30 minutes The mixture was stirred for 3 hours at ca. 80° C After cooling to room temperature the mixture was concentrated in vacuo washed with water (50 ml), saturated sodium carbonate aqueous solution (50 ml) and water (50 ml) The organic layer was dried over sodium sulfate filtered concentrated in vacuo

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In a round-bottomed flask, phosphorous oxybromide (5.0 g, 17.4 mmol and 4-tert-butylpyridine N-oxide (0.85 g, 5.34 mmol) were dissolved in 1,2-dichloroethane (35 mL). The reaction mixture was stirred at 70° C. overnight then cooled to room temperature and slowly poured onto ice. Sodium hydroxide (50% solution in water) was added slowly until pH˜10. The mixture was then extracted three times with ˜100 mL dichloromethane. The organic layers were combined, dried over sodium sulfate, filtered and concentrated. The residue was absorbed on 4 g SiO2 and chromatographed over 24 g SiO2 with EtOAc/Hexanes (gradient: 0-10% EtOAc). All fractions containing product were combined and concentrated to give 157 mg (14%) of 2-bromo-4-tert-butyl pyridine as a colorless oil. then cooled to room temperature slowly poured onto ice The mixture was then extracted three times with ˜100 mL dichloromethane dried over sodium sulfate filtered concentrated The residue was absorbed on 4 g SiO2 chromatographed over 24 g SiO2 with EtOAc/Hexanes (gradient: 0-10% EtOAc) All fractions containing product concentrated

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

実験手順: In a round-bottomed flask, 4-tert-butylpyridine (1.5 g, 11.1 mmol) was dissolved in acetic acid (9 mL) and hydrogen peroxide (30 wt. % solution in water, 6.0 mL, 58.7 mmol) was added. The colorless solution was stirred at 90° C. overnight. The reaction mixture was cooled to room temperature and concentrated. The residue was poured onto ˜40 mL saturated Na2CO3 solution and extracted with 100 mL dichloromethane (2×). The organic layers were combined, dried over sodium sulfate, filtered and concentrated to afford 1.75 g (99%) of 4-tert-butylpyridine N-oxide as light yellow solid. The reaction mixture was cooled to room temperature concentrated The residue was poured onto ˜40 mL saturated Na2CO3 solution extracted with 100 mL dichloromethane (2×) dried over sodium sulfate filtered concentrated

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

実験手順: 4-t-Butyl-pyridine N-oxide (11.0 g, 72.9 mmole) is dissolved in 200 ml dichloromethane in a 500 ml one neck round bottom flask under nitrogen. The solution is treated with trimethyloxonium tetrafluoroborate (10.8 g, 72.9 mmole), is stirred 1h at room temperature, and the volatiles are removed in vacuo. The solid residue is dissolved in 200 ml methanol in a 500 ml one neck round bottom flask. The solution is heated to reflux, is treated with ammonium persulfate (3.3 g, 14.5 mmole) in 15 ml water, and the reaction mixture is vigorously refluxed for 30 min. The reaction is treated with a second lot of ammonium persulfate (1.65 g, 7.2 mmole) in 7 ml water and is refluxed for an additional 1 h. The reaction is cooled and the bulk of the methanol is removed in vacuo. The residue is diluted with 300 ml conc ammonium hydroxide and the mixture is extracted with 4×100 ml dichloromethane. The combined organics are dried over potassium carbonate and are concentrated in vacuo to a yellow oil. The crude material is chromatographed over 400 g silica gel (230-400 mesh), eluting with 40% acetone/hexane, while collecting 50 ml fractions. Fractions 26-52 are combined and concentrated to afford 8.79 g (73%) of 4-t-Butyl-2-hydroxymethyl-pyridine as a yellow oil. the volatiles are removed in vacuo The solid residue is dissolved in 200 ml methanol in a 500 ml one neck round bottom flask The solution is heated to reflux the reaction mixture is vigorously refluxed for 30 min is refluxed for an additional 1 h The reaction is cooled the bulk of the methanol is removed in vacuo The residue is diluted with 300 ml conc ammonium hydroxide the mixture is extracted with 4×100 ml dichloromethane The combined organics are dried over potassium carbonate are concentrated in vacuo to a yellow oil The crude material is chromatographed over 400 g silica gel (230-400 mesh) eluting with 40% acetone/hexane while collecting 50 ml fractions concentrated

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

実験手順: A mixture of 8.00 g (53 mmol) of 4-t-butylpyridine N-oxide and 6.7 g (53 mmol) of dimethylsulfuric acid was stirred at 70° to 80° C. for 3 hours. After cooling, the mixture was dissolved in 60 ml of an ethanol-water mixture. While the mixture was stirred at 10° C. or lower, a solution of 6.9 g (0.11 mol) of potassium cyanide in 20 ml of water was dropwise added, followed further by stirring at the same temperature for one hour and at room temperature for 1.5 hours. After an addition of 200 ml of water, the mixture was stirred with chloroform, dried over anhydrous sodium sulfate, and then concentrated under a reduced pressure. Separation by silica gel column chromatography (ethyl acetate:hexane=1:4 for the first time, 1:9 for the second time) gave 2.00 g of an oily product (yield 23.6%). After cooling While the mixture was stirred at 10° C. by stirring at the same temperature for one hour and at room temperature for 1.5 hours dried over anhydrous sodium sulfate concentrated under a reduced pressure Separation by silica gel column chromatography (ethyl acetate

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In a reaction flask, 4-(tert-butyl)pyridine (13.5 g, 99.8 mmol) was dissolved in 70 ml of acetic acid (1.29 mmol), and 30 ml of hydrogen peroxide (H2O2) (30%, 0.30 mol) was then slowly added to obtain a mixture. The mixture was heated to 80° C. for reaction for 24 hours, and the temperature was then slowly reduced to 20° C. The reaction flask was vacuum pumped to remove solvents from the mixture, followed by addition of a sodium hydroxide aqueous solution to adjust the pH of the mixture to 8. Next, the mixture was washed several times with dichloromethane and with deionized water to collect an organic layer, and the organic layer was dehydrated using sodium sulfate (Na2SO4). The solvent was then removed from the organic layer, followed by vacuum drying, thereby obtaining light yellow solids (13 g, 87% yield), which was Compound L4-1 having a chemical structure represented by to obtain a mixture was then slowly reduced to 20° C to remove solvents from the mixture followed by addition of a sodium hydroxide aqueous solution Next, the mixture was washed several times with dichloromethane with deionized water to collect an organic layer The solvent was then removed from the organic layer drying

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

実験手順: To trimethylsilylcyanide (25.0 ml, 187.5 mmol) was added a solution of 4-tert-butylpyridine-N-oxide (Description 3; 22.68 g, 150 mmol) in anhydrous dichloromethane (200 ml). To this mixture was added dropwise a solution of dimethyl carbamoyl chloride (17.26 ml, 187.5 mmol) in anhydrous dichloromethane (50 ml). The reaction mixture was stirred at room temperature for 24 hours. A solution of 10% aqueous K2CO3 (200 ml) was added dropwise and the resulting mixture stirred for 10 minutes. The organic layer was separated and the aqueous layer extracted with 2 further portions of dichloromethane (100 ml). The combined organic layers were dried (Na2SO4) and evaporated to give the title compound (24 g, 100%). the resulting mixture stirred for 10 minutes The organic layer was separated the aqueous layer extracted with 2 further portions of dichloromethane (100 ml) The combined organic layers were dried (Na2SO4) evaporated

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

実験手順: To a solution of 4-tert-butylpyridine (44.3 ml, 300 mmol) in glacial acetic acid (200 ml) was added hydrogen peroxide (37.1 ml of a 27.5% aqueous solution, 300 mmol), and the resulting mixture heated at reflux overnight. The cooled mixture was evaporated to dryness. The residue was dissolved in dichloromethane (200 ml), and washed with brine (50 ml), then dried (Na2SO4) and evaporated to give the title compound (40 g, 88%) as a white solid. heated at reflux overnight The cooled mixture was evaporated to dryness The residue was dissolved in dichloromethane (200 ml) washed with brine (50 ml) dried (Na2SO4) evaporated

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To stirred dimethyl sulfate (6.70 g) was added slowly 4-tert-butyl-1-oxypyridine (8.0 g) at ca. 10° C. in an ice-water bath and the mixture was stirred for 3 hours at 80° C. After cooling to room temperature, to the mixture was added a mixture of ethanol and water (1:1, 60 ml) under stirring. To the mixture was added dropwise an aqueous solution of potassium cyanate (6.9 g in 20 ml of water) below 10° C. and stirring for 1 hour under the same condition, and then overnight at room temperature. To the resultant mixture was added 150 ml of water and the resultant mixture was extracted with CHCl3. The organic layer was dried over sodium sulfate, filtered and concentrated in vacuo. A crude compound was purified by column chromatography on silica gel with a mixture of ethyl acetate and n-hexane to give 4-tert-butyl-2-cyanopyridine (4.6 g) as a yellow oil. After cooling to room temperature, to the mixture was added under stirring stirring for 1 hour under the same condition overnight at room temperature the resultant mixture was extracted with CHCl3 The organic layer was dried over sodium sulfate filtered concentrated in vacuo A crude compound was purified by column chromatography on silica gel with a mixture of ethyl acetate and n-hexane

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

実験手順: To a stirred solution of 4-tert-butylpyridine (19.0 g) in acetic acid (90 ml) was added dropwise 50% of hydrogen peroxide aqueous solution (20 ml) at room temperature and stirred for 30 minutes under the same condition. The mixture was stirred for 3 hours at ca.80° C. After cooling to room temperature, to the mixture was added dropwise another 20 ml of 50% hydrogen peroxide aqueous solution and stirred for 30 minutes. The mixture was stirred for 3 hours at ca. 80° C. After cooling to room temperature, the mixture was concentrated in vacuo. The residue was taken up with chloroform, and washed with water (50 ml), saturated sodium carbonate aqueous solution (50 ml) and water (50 ml). The organic layer was dried over sodium sulfate, filtered and concentrated in vacuo to give 4-tert-butyl-1-oxypyridine, which was crystallized by isopropyl ether as a colorless powder (19.1 g). The mixture was stirred for 3 hours at ca 80° C stirred for 30 minutes The mixture was stirred for 3 hours at ca. 80° C After cooling to room temperature the mixture was concentrated in vacuo washed with water (50 ml), saturated sodium carbonate aqueous solution (50 ml) and water (50 ml) The organic layer was dried over sodium sulfate filtered concentrated in vacuo