2-methylpropyl nitrate

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

実験手順: Potassium tert-butoxide (7.6 g, 67.8 mM), (20S)-20-hydroxymethylpregn-4-en-3-one (6.6 g, 20 mM) in tert-butanol is heated at reflux temperature for 60 minutes under an argon atmosphere. Isobutylnitrate (2.34 ml, 20 mM) is then added in one continuous portion. After 20 minutes of further refluxing, the reaction vessel is cooled to room temperature. Acetic acid (10 ml) is then added, and the reaction vessel stirred for 18 hours, after which the combination is diluted with dichloromethane (200 mL). The solids are removed, washed, and recombined with the washing residue and subsequently purified as described in Example 1 to give crystallized (20S)-20-hydroxymethyl-4-nitropregn-4-en-3-one. at reflux temperature for 60 minutes under an argon atmosphere The solids are removed washed subsequently purified to give crystallized (20S)-20-hydroxymethyl-4-nitropregn-4-en-3-one

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

実験手順: Using a similar nitration procedure to that described in Example 9, but starring from acid (C) and using isobutyl nitrate in place of isoamyl nitrate, there was obtained 2-t-butyl-5,5-dimethyl- 2-[2-(nitromethylthio)thien-5-yl]-1,3-dioxane (D) as an oil, in 47% yield; NMR: 0.6(s, 3H), 0.96(s, 9H), 1.2(s, 3H), 3.36(dd, 2H), 3.55(d, 2H), 5.32(s, 2H), 6.82(d, 1H), 7.22(d, 1H); m/e (chemical ionisation) 346 (M+H)+.

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

実験手順: Potassium tert-butoxide (7.6 g, 67.8 mM), (20S)-20-hydroxymethylpregn-4-en-3-one (6.6 g, 20 mM) in tert-butanol is heated at reflux temperature for 60 minutes under an argon atmosphere. Isobutylnitrate (2.34 ml, 20 mM) is then added in one continuous portion. After 20 minutes of further refluxing, the reaction vessel is cooled to room temperature. Acetic acid (10 ml) is then added, and the reaction vessel stirred for 18 hours, after which the combination is diluted with dichloromethane (200 mL). The solids are removed, washed, and recombined with the washing residue and subsequently purified as described in Example 1 to give crystallized (20S)-20-hydroxymethyl-4-nitropregn-4-en-3-one. at reflux temperature for 60 minutes under an argon atmosphere The solids are removed washed subsequently purified to give crystallized (20S)-20-hydroxymethyl-4-nitropregn-4-en-3-one

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

実験手順: Potassium tert-butoxide (7.6 g, 67.8 mM), (20S)-20-hydroxymethylpregn-4-en-3-one (6.6 g, 20 mM) in tert-butanol is heated at reflux temperature for 60 minutes under an argon atmosphere. Isobutylnitrate (2.34 ml, 20 mM) is then added in one continuous portion. After 20 minutes of further refluxing, the reaction vessel is cooled to room temperature. Acetic acid (10 ml) is then added, and the reaction vessel stirred for 18 hours, after which the combination is diluted with dichloromethane (200 mL). The solids are removed, washed, and recombined with the washing residue and subsequently purified as described in Example 1 to give crystallized (20S)-20-hydroxymethyl-4-nitropregn-4-en-3-one. at reflux temperature for 60 minutes under an argon atmosphere The solids are removed washed subsequently purified to give crystallized (20S)-20-hydroxymethyl-4-nitropregn-4-en-3-one

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

実験手順: Ac2O (0.579 ml, 6.14 mmol) was added to a stirred mixture of KOAc (361 mg, 3.68 mmol) and methyl 3-amino-4-ethylbenzoate (550mg, 3.07 mmol) in CHCl3 (5 ml) and the mixture was stirred at 90° C. for 2 h. KOAc (361 mg, 3.68 mmol), 18-crown-6 ether (81 mg, 0.307 mmol) and isobutylnitrate (719 mg, 6.14 mmol) were added thereto at room temperature and the mixture was further stirred at 90° C. for 2 h. The reaction mixtuer was diluted with chloroform and H2O, the organic layer was washed with water, brine, and dried over MgSO4. After filteration and evaporation, the residue was diluted with THF (5.00 ml) and MeOH (5.00 ml), and K2CO3 (848 mg, 6.14 mmol) was added thereto at room temperature. After the mixture was stirred for 2 h. at room temperature, CHCl3 and H2O was added thereto. The organic layer was washed with H2O, brine, and dried over MgSO4. After filteration and evaporation, the reside was puritied by silicagel column chromatography (hexane/EtOAc) to give intended compound as a pale brown solid. at room temperature and the mixture was further stirred at 90° C. for 2 h the organic layer was washed with water, brine dried over MgSO4 After filteration and evaporation was added at room temperature After the mixture was stirred for 2 h. at room temperature The organic layer was washed with H2O, brine dried over MgSO4 After filteration and evaporation to give

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

実験手順: Ac2O (0.579 ml, 6.14 mmol) was added to a stirred mixture of KOAc (361 mg, 3.68 mmol) and methyl 3-amino-4-ethylbenzoate (550mg, 3.07 mmol) in CHCl3 (5 ml) and the mixture was stirred at 90° C. for 2 h. KOAc (361 mg, 3.68 mmol), 18-crown-6 ether (81 mg, 0.307 mmol) and isobutylnitrate (719 mg, 6.14 mmol) were added thereto at room temperature and the mixture was further stirred at 90° C. for 2 h. The reaction mixtuer was diluted with chloroform and H2O, the organic layer was washed with water, brine, and dried over MgSO4. After filteration and evaporation, the residue was diluted with THF (5.00 ml) and MeOH (5.00 ml), and K2CO3 (848 mg, 6.14 mmol) was added thereto at room temperature. After the mixture was stirred for 2 h. at room temperature, CHCl3 and H2O was added thereto. The organic layer was washed with H2O, brine, and dried over MgSO4. After filteration and evaporation, the reside was puritied by silicagel column chromatography (hexane/EtOAc) to give intended compound as a pale brown solid. at room temperature and the mixture was further stirred at 90° C. for 2 h the organic layer was washed with water, brine dried over MgSO4 After filteration and evaporation was added at room temperature After the mixture was stirred for 2 h. at room temperature The organic layer was washed with H2O, brine dried over MgSO4 After filteration and evaporation to give

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

実験手順: Potassium tert-butoxide (7.6 g, 67.8 mM), (20S)-20-hydroxymethylpregn-4-en-3-one (6.6 g, 20 mM) in tert-butanol is heated at reflux temperature for 60 minutes under an argon atmosphere. Isobutylnitrate (2.34 ml, 20 mM) is then added in one continuous portion. After 20 minutes of further refluxing, the reaction vessel is cooled to room temperature. Acetic acid (10 ml) is then added, and the reaction vessel stirred for 18 hours, after which the combination is diluted with dichloromethane (200 mL). The solids are removed, washed, and recombined with the washing residue and subsequently purified as described in Example 1 to give crystallized (20S)-20-hydroxymethyl-4-nitropregn-4-en-3-one. at reflux temperature for 60 minutes under an argon atmosphere The solids are removed washed subsequently purified to give crystallized (20S)-20-hydroxymethyl-4-nitropregn-4-en-3-one

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

実験手順: Potassium tert-butoxide (7.6 g, 67.8 mM), (20S)-20-hydroxymethylpregn-4-en-3-one (6.6 g, 20 mM) in tert-butanol is heated at reflux temperature for 60 minutes under an argon atmosphere. Isobutylnitrate (2.34 ml, 20 mM) is then added in one continuous portion. After 20 minutes of further refluxing, the reaction vessel is cooled to room temperature. Acetic acid (10 ml) is then added, and the reaction vessel stirred for 18 hours, after which the combination is diluted with dichloromethane (200 mL). The solids are removed, washed, and recombined with the washing residue and subsequently purified as described in Example 1 to give crystallized (20S)-20-hydroxymethyl-4-nitropregn-4-en-3-one. at reflux temperature for 60 minutes under an argon atmosphere The solids are removed washed subsequently purified to give crystallized (20S)-20-hydroxymethyl-4-nitropregn-4-en-3-one

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

実験手順: 1 g (5.2 mmol) of 5H-dibenz(b,f)azepine was suspended in 40 ml of dry ether and 9.7 ml (15.5 mmol) of a 1.6M solution of n-butyllithium in hexane was dropped thereinto under stirring at room temperature. After 24 hours, the reaction mixture was cooled in a dry ice-acetone bath and 2 ml of a solution of 0.93 g (7.8 mmol) of isobutyl nitrate in dry ether was dropped thereinto. After stirring at room temperature for 30 minutes, 2 ml of acetic acid was added thereto. Then the reaction mixture was poured into 50 ml of water and extracted with ethyl acetate. The organic layer was washed with water, dried over magnesium sulfate and concentrated. Then the residue was purified by silica gel column chromatography to thereby give 4-nitro-5H-dibenz(b,f)azepine. This product was dissolved in 50 ml of tetrahydrofuran and 1 g of zinc dust was added. Under stirring, conc. hydrochloric acid was dropped thereinto. When the reaction mixture turned from reddish brown into pale yellow, the addition was ceased and the formed insoluble matters were filtered off. The filtrate was made basic by adding diluted aqueous ammonia and then extracted with ethyl acetate. The organic layer was washed with water, dried over magnesium sulfate and concentrated and the residue was purified by silica gel column chromatography. Thus 45 mg of the title compound was obtained. the reaction mixture was cooled in a dry ice-acetone bath After stirring at room temperature for 30 minutes extracted with ethyl acetate The organic layer was washed with water dried over magnesium sulfate concentrated Then the residue was purified by silica gel column chromatography to thereby give 4-nitro-5H-dibenz(b,f)azepine This product was dissolved in 50 ml of tetrahydrofuran 1 g of zinc dust was added Under stirring conc. hydrochloric acid was dropped the addition the formed insoluble matters were filtered off by adding diluted aqueous ammonia extracted with ethyl acetate The organic layer was washed with water dried over magnesium sulfate concentrated the residue was purified by silica gel column chromatography

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

実験手順: Potassium tert-butoxide (7.6 g, 67.8 mM), (20S)-20-hydroxymethylpregn-4-en-3-one (6.6 g, 20 mM) in tert-butanol is heated at reflux temperature for 60 minutes under an argon atmosphere. Isobutylnitrate (2.34 ml, 20 mM) is then added in one continuous portion. After 20 minutes of further refluxing, the reaction vessel is cooled to room temperature. Acetic acid (10 ml) is then added, and the reaction vessel stirred for 18 hours, after which the combination is diluted with dichloromethane (200 mL). The solids are removed, washed, and recombined with the washing residue and subsequently purified as described in Example 1 to give crystallized (20S)-20-hydroxymethyl-4-nitropregn-4-en-3-one. at reflux temperature for 60 minutes under an argon atmosphere The solids are removed washed subsequently purified to give crystallized (20S)-20-hydroxymethyl-4-nitropregn-4-en-3-one

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

実験手順: Using a similar nitration procedure to that described in Example 9, but starring from acid (C) and using isobutyl nitrate in place of isoamyl nitrate, there was obtained 2-t-butyl-5,5-dimethyl- 2-[2-(nitromethylthio)thien-5-yl]-1,3-dioxane (D) as an oil, in 47% yield; NMR: 0.6(s, 3H), 0.96(s, 9H), 1.2(s, 3H), 3.36(dd, 2H), 3.55(d, 2H), 5.32(s, 2H), 6.82(d, 1H), 7.22(d, 1H); m/e (chemical ionisation) 346 (M+H)+.

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

実験手順: Potassium tert-butoxide (7.6 g, 67.8 mM), (20S)-20-hydroxymethylpregn-4-en-3-one (6.6 g, 20 mM) in tert-butanol is heated at reflux temperature for 60 minutes under an argon atmosphere. Isobutylnitrate (2.34 ml, 20 mM) is then added in one continuous portion. After 20 minutes of further refluxing, the reaction vessel is cooled to room temperature. Acetic acid (10 ml) is then added, and the reaction vessel stirred for 18 hours, after which the combination is diluted with dichloromethane (200 mL). The solids are removed, washed, and recombined with the washing residue and subsequently purified as described in Example 1 to give crystallized (20S)-20-hydroxymethyl-4-nitropregn-4-en-3-one. at reflux temperature for 60 minutes under an argon atmosphere The solids are removed washed subsequently purified to give crystallized (20S)-20-hydroxymethyl-4-nitropregn-4-en-3-one