heptane-2,6-dione

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

Procedure: An aqueous solution (32 ml) of heptane-2,6-dione (4.96 g, 38.7 mmol) and acetonedicarboxylic acid (10.74 g, 73.5 mmol) was injected into a sealed tube, and 27 M KOH (6 ml), an ammonium chloride (6.20 g, 116 mmol) aqueous solution (60 ml), and sodium acetate (3.81 g, 46.4 mmol) were added in order under ice-cooled condition. The mixture was then brought to pH 9 with a 1 g/ml KOH aqueous solution. The reaction liquid was stirred inside the sealed tube in the dark at room temperature for 3 days. A 10% hydrochloric acid aqueous solution was slowly dropped until the carbon dioxide gas generation went to completion, and the mixture was washed with dichloromethane. After a separation procedure, the aqueous layer was brought to basic pH with a 10% sodium hydroxide aqueous solution, and extracted with dichloromethane. The organic layer was dried over potassium carbonate, concentrated under reduced pressure, and purified by silica gel column chromatography to give 1,5-dimethyl-9-azabicyclo[3.3.1]nonan-3-one (1.84 g, 28%). cooled condition The reaction liquid the mixture was washed with dichloromethane After a separation procedure extracted with dichloromethane The organic layer was dried over potassium carbonate concentrated under reduced pressure purified by silica gel column chromatography

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

Procedure: An aqueous solution (32 ml) of heptane-2,6-dione (4.96 g, 38.7 mmol) and acetonedicarboxylic acid (10.74 g, 73.5 mmol) was injected into a sealed tube, and 27 M KOH (6 ml), an ammonium chloride (6.20 g, 116 mmol) aqueous solution (60 ml), and sodium acetate (3.81 g, 46.4 mmol) were added in order under ice-cooled condition. The mixture was then brought to pH 9 with a 1 g/ml KOH aqueous solution. The reaction liquid was stirred inside the sealed tube in the dark at room temperature for 3 days. A 10% hydrochloric acid aqueous solution was slowly dropped until the carbon dioxide gas generation went to completion, and the mixture was washed with dichloromethane. After a separation procedure, the aqueous layer was brought to basic pH with a 10% sodium hydroxide aqueous solution, and extracted with dichloromethane. The organic layer was dried over potassium carbonate, concentrated under reduced pressure, and purified by silica gel column chromatography to give 1,5-dimethyl-9-azabicyclo[3.3.1]nonan-3-one (1.84 g, 28%). cooled condition The reaction liquid the mixture was washed with dichloromethane After a separation procedure extracted with dichloromethane The organic layer was dried over potassium carbonate concentrated under reduced pressure purified by silica gel column chromatography

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

Procedure: N,O-Dimethylhydroxylamine hydrochloride (42 g, 431 mmol) was added to a dichloromethane (500 ml) solution of glutaryl chloride (25 ml, 196 mmol) at room temperature, and pyridine (95 ml, 1.18 mol) was dropped under ice-cooled condition. After being stirred at room temperature for 2 hours, the reaction mixture was celite filtered. The filtrate was concentrated under reduced pressure, and diethyl ether (300 ml) was added. The mixture was celite filtered again, and concentrated under reduced pressure to give a Weinreb diamide product. The Weinreb diamide product was dissolved in tetrahydrofuran (500 ml), and a 3 M diethyl ether solution (160 ml, 0.470 mol) methylmagnesium bromide was slowly dropped under ice-cooled condition. After being stirred at room temperature for 4 hours, the mixture was brought back to ice-cooled condition, and water was slowly added. After extraction with ethyl acetate, the reaction liquid was washed with saturated brine. The organic layer was dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was then purified by silica gel column chromatography to give heptane-2,6-dione (20.3 g, 81%). cooled condition was slowly added After extraction with ethyl acetate the reaction liquid was washed with saturated brine The organic layer was dried over magnesium sulfate the solvent was evaporated under reduced pressure The residue was then purified by silica gel column chromatography

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

Procedure: An aqueous solution (32 ml) of heptane-2,6-dione (4.96 g, 38.7 mmol) and acetonedicarboxylic acid (10.74 g, 73.5 mmol) was injected into a sealed tube, and 27 M KOH (6 ml), an ammonium chloride (6.20 g, 116 mmol) aqueous solution (60 ml), and sodium acetate (3.81 g, 46.4 mmol) were added in order under ice-cooled condition. The mixture was then brought to pH 9 with a 1 g/ml KOH aqueous solution. The reaction liquid was stirred inside the sealed tube in the dark at room temperature for 3 days. A 10% hydrochloric acid aqueous solution was slowly dropped until the carbon dioxide gas generation went to completion, and the mixture was washed with dichloromethane. After a separation procedure, the aqueous layer was brought to basic pH with a 10% sodium hydroxide aqueous solution, and extracted with dichloromethane. The organic layer was dried over potassium carbonate, concentrated under reduced pressure, and purified by silica gel column chromatography to give 1,5-dimethyl-9-azabicyclo[3.3.1]nonan-3-one (1.84 g, 28%). cooled condition The reaction liquid the mixture was washed with dichloromethane After a separation procedure extracted with dichloromethane The organic layer was dried over potassium carbonate concentrated under reduced pressure purified by silica gel column chromatography

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

Procedure: N,O-Dimethylhydroxylamine hydrochloride (42 g, 431 mmol) was added to a dichloromethane (500 ml) solution of glutaryl chloride (25 ml, 196 mmol) at room temperature, and pyridine (95 ml, 1.18 mol) was dropped under ice-cooled condition. After being stirred at room temperature for 2 hours, the reaction mixture was celite filtered. The filtrate was concentrated under reduced pressure, and diethyl ether (300 ml) was added. The mixture was celite filtered again, and concentrated under reduced pressure to give a Weinreb diamide product. The Weinreb diamide product was dissolved in tetrahydrofuran (500 ml), and a 3 M diethyl ether solution (160 ml, 0.470 mol) methylmagnesium bromide was slowly dropped under ice-cooled condition. After being stirred at room temperature for 4 hours, the mixture was brought back to ice-cooled condition, and water was slowly added. After extraction with ethyl acetate, the reaction liquid was washed with saturated brine. The organic layer was dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was then purified by silica gel column chromatography to give heptane-2,6-dione (20.3 g, 81%). cooled condition was slowly added After extraction with ethyl acetate the reaction liquid was washed with saturated brine The organic layer was dried over magnesium sulfate the solvent was evaporated under reduced pressure The residue was then purified by silica gel column chromatography