1,3-dimethylpiperidin-4-one

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:-70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The 3-bromo-i-propoxybenzene (200 g, 0.08703 mol) was combined with THF (540 ml) under nitrogen and cooled to about -75° C. n-Butyl lithium (565 ml, 0.8306 mol) was added dropwise while maintaining the mixture at less than -70° C. After 2 hours 1,3-Dimethyl-4-piperidone (106.7 g, 0.8389 mol) was added while maintaining the temperature of the mixture between -80° C. and -70° C. After stirring 2 hours at -70° C., the reaction mixture was then added to 6N HCl (280 ml) while maintaining the temperature at 20°-25° C. The pH was adjusted to 1 with 12N HCl. The aqueous layer containing product was separated and heptane (320 ml) was added along with 50% NaOH (48 ml, pH=13-14) and the resulting mixture allowed to stand overnight. The mixture was heated to 45°- 50° C. and the upper layer was separated. The remaining aqueous layer was extracted with heptane (320 ml) at 45°-50° C. The combined organic fractions were washed with de-ionized water (120 ml) at 45°-50° C. The resulting organic layer was vacuum distilled at a pot temperature of about 55° C. at 100 mmHg. Crystallization from heptane and drying provided 151.8 g of 3-(3-i-propoxyphenyl)-1,3-dimethyl-4-hydroxypiperidine. Melting point 75.0°-76.0° C. was added dropwise while maintaining the mixture at less than -70° C while maintaining the temperature of the mixture between -80° C. and -70° C while maintaining the temperature at 20°-25° C The aqueous layer containing product was separated heptane (320 ml) was added along with 50% NaOH (48 ml, pH=13-14) to stand overnight The mixture was heated to 45°- 50° C. the upper layer was separated The remaining aqueous layer was extracted with heptane (320 ml) at 45°-50° C The combined organic fractions were washed with de-ionized water (120 ml) at 45°-50° C distilled at a pot temperature of about 55° C. at 100 mmHg Crystallization from heptane drying

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

Procedure: Beginning with 0.97 gm (6.4 mMol) 6-chloro-1H-indole and 1.6 gm (13.0 mMol) 1,3-dimethyl-4-piperidone, 1.05 gm (63%) of the title compound were recovered as a crystalline solid.

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

Procedure: 50 ml of a bimolar solution of n-butyl lithium in hexane is added dropwise within 30 minutes, at a reaction temperature of -5°, to a solution of 11.8 g of benzofuran in 100 ml of diethyl ether. The solution is then stirred for a further hour at 0°. There is thereupon made within 15 minutes a dropwise addition of a solution of 1,3-dimethyl-4-piperidone in 50 ml of abs. diethyl ether. The reaction temperature is maintained at 0° by external cooling. The reaction solution is subsequently stirred for a further 15 hours at room temperature. It is then poured, with stirring, onto 200 g of ice, and the aqueous phase extracted three times with 500 ml of ethyl acetate each time. The combined organic extracts are dried over sodium sulphate, filtered, and concentrated by evaporation. The residue is dissolved in 500 ml of 2N hydrochloric acid and the acid solution washed with ether. The aqueous solution is thereupon adjusted by addition of 10% sodium hydroxide solution to pH 12, and extracted with 1 liter of chloroform. The chloroform solution is dried with sodium sulphate, filtered off under suction, and concentrated by evaporation to obtain 4-(2-benzofuranyl)-1,3-dimethyl-4-piperidinol, which melts at 128°-130° after recrystallisation from hexane. The reaction temperature is maintained at 0° by external cooling The reaction solution is subsequently stirred for a further 15 hours at room temperature It is then poured the aqueous phase extracted three times with 500 ml of ethyl acetate each time The combined organic extracts are dried over sodium sulphate filtered concentrated by evaporation The residue is dissolved in 500 ml of 2N hydrochloric acid the acid solution washed with ether The aqueous solution is thereupon adjusted by addition of 10% sodium hydroxide solution to pH 12 extracted with 1 liter of chloroform The chloroform solution is dried with sodium sulphate filtered off under suction concentrated by evaporation

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 1,3-dimethyl-piperidin-4-one (0.1 g, 0.787 mmol) in mixture of 1,4 dioxane (2 mL) and water (0.1 mL) was added crushed KOH (44 mg, 0.787 mmol). The reaction mixture was stirred at 25° C. for 10 min. To this was added 1-phenylprop-2-en-1-one (103 mg, 0.787 mmol) dropwise. The reaction mixture was stirred at 25° C. for 2 h. The reaction mixture was concentrated under reduced pressure and the residue was diluted with water (10 mL) and EtOAc (20 mL), the organic layer was separated, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting crude product was purified by column chromatography on neutral alumina (eluted with EtOAc:Hexanes, 1:99) to afford 1,3-dimethyl-3-(3-oxo-3-phenyl-propyl)-piperidin-4-one as an oil (22 mg). was added The reaction mixture was stirred at 25° C. for 2 h The reaction mixture was concentrated under reduced pressure the residue was diluted with water (10 mL) and EtOAc (20 mL) the organic layer was separated dried over anhydrous sodium sulfate concentrated under reduced pressure The resulting crude product was purified by column chromatography on neutral alumina (eluted with EtOAc:Hexanes, 1:99)

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

Procedure: 1,3-Dimethyl-piperidin-4-one (6 g, 47.24 mmol) was dissolved in 20 mL DMF and sodium hydride (2.07 g, 51.95 mmol) was added portionwise at 0° C. under nitrogen atmosphere. This was followed by dropwise addition of allyl bromide (5.71 g, 47.19 mmol) in 4 mL DMF at 0° C. under nitrogen atmosphere. The reaction mixture was stirred at RT for 15 min, quenched with ice-water and extracted with EtOAc (3×100 mL). The organic layer was washed with water (3×100 mL), dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography (silica gel, 100-200 mesh) eluting with 7% EtOAc in hexane to obtain 3.2 g of 3-allyl-1,3-dimethyl-piperidin-4-one. quenched with ice-water extracted with EtOAc (3×100 mL) The organic layer was washed with water (3×100 mL) dried over sodium sulfate concentrated under reduced pressure The residue was purified by column chromatography (silica gel, 100-200 mesh) eluting with 7% EtOAc in hexane

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

Procedure: 1,3-Dimethyl-piperidin-4-one (6 g, 47.24 mmol) was dissolved in 20 mL DMF and sodium hydride (2.07 g, 51.95 mmol) was added portionwise at 0° C. under nitrogen atmosphere. This was followed by dropwise addition of allyl bromide (5.71 g, 47.19 mmol) in 4 mL DMF at 0° C. under nitrogen atmosphere. The reaction mixture was stirred at RT for 15 min, quenched with ice-water and extracted with EtOAc (3×100 mL). The organic layer was washed with water (3×100 mL), dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography (silica gel, 100-200 mesh) eluting with 7% EtOAc in hexane to obtain 3.2 g of 3-allyl-1,3-dimethyl-piperidin-4-one. quenched with ice-water extracted with EtOAc (3×100 mL) The organic layer was washed with water (3×100 mL) dried over sodium sulfate concentrated under reduced pressure The residue was purified by column chromatography (silica gel, 100-200 mesh) eluting with 7% EtOAc in hexane

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

Procedure: 1,3-Dimethyl-piperidin-4-one (6 g, 47.24 mmol) was dissolved in DMF (20 mL) and sodium hydride (2.07 g, 51.95 mmol) was added portionwise at 0° C. under nitrogen atmosphere. This was followed by dropwise addition of allyl bromide (5.71 g, 47.19 mmol) in DMF (4 mL) at 0° C. under nitrogen atmosphere. The reaction mixture was stirred at RT for 15 min, quenched with ice-water and extracted with EtOAc (3×100 mL). The organic layer was washed with water (3×100 mL), dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography (silica gel, 100-200 mesh) eluting with 7% EtOAc in hexane to obtain 3.2 g of 3-allyl-1,3-dimethyl-piperidin-4-one. quenched with ice-water extracted with EtOAc (3×100 mL) The organic layer was washed with water (3×100 mL) dried over sodium sulfate concentrated under reduced pressure The residue was purified by column chromatography (silica gel, 100-200 mesh) eluting with 7% EtOAc in hexane

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

Procedure: 1,3-Dimethyl-piperidin-4-one (6 g, 47.24 mmol) was dissolved in 20 mL DMF and sodium hydride (2.07 g, 51.95 mmol) was added portionwise at 0° C. under nitrogen atmosphere. This was followed by dropwise addition of allyl bromide (5.71 g, 47.19 mmol) in 4 mL DMF at 0° C. under nitrogen atmosphere. The reaction mixture was stirred at RT for 15 min, quenched with ice-water and extracted with EtOAc (3×100 mL). The organic layer was washed with water (3×100 mL), dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography (silica gel, 100-200 mesh) eluting with 7% EtOAc in hexane to obtain 3.2 g of 3-allyl-1,3-dimethyl-piperidin-4-one. quenched with ice-water extracted with EtOAc (3×100 mL) The organic layer was washed with water (3×100 mL) dried over sodium sulfate concentrated under reduced pressure The residue was purified by column chromatography (silica gel, 100-200 mesh) eluting with 7% EtOAc in hexane

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

Procedure: 1,3-Dimethyl-piperidin-4-one (6 g, 47.24 mmol) was dissolved in 20 mL DMF and sodium hydride (2.07 g, 51.95 mmol) was added portionwise at 0° C. under nitrogen atmosphere. This was followed by dropwise addition of allyl bromide (5.71 g, 47.19 mmol) in 4 mL DMF at 0° C. under nitrogen atmosphere. The reaction mixture was stirred at RT for 15 min, quenched with ice-water and extracted with EtOAc (3×100 mL). The organic layer was washed with water (3×100 mL), dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography (silica gel, 100-200 mesh) eluting with 7% EtOAc in hexane to obtain 3.2 g of 3-allyl-1,3-dimethyl-piperidin-4-one. quenched with ice-water extracted with EtOAc (3×100 mL) The organic layer was washed with water (3×100 mL) dried over sodium sulfate concentrated under reduced pressure The residue was purified by column chromatography (silica gel, 100-200 mesh) eluting with 7% EtOAc in hexane

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

Procedure: 1,3-Dimethyl-piperidin-4-one (6 g, 47.24 mmol) was dissolved in 20 mL DMF and sodium hydride (2.07 g, 51.95 mmol) was added portionwise at 0° C. under nitrogen atmosphere. This was followed by dropwise addition of allyl bromide (5.71 g, 47.19 mmol) in 4 mL DMF at 0° C. under nitrogen atmosphere. The reaction mixture was stirred at RT for 15 min, quenched with ice-water and extracted with EtOAc (3×100 mL), The organic layer was washed with water (3×100 mL), dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography (silica gel, 100-200 mesh) eluting with 7% EtOAc in hexane to obtain 3.2 g of 3-allyl-1,3-dimethyl-piperidin-4-one. quenched with ice-water extracted with EtOAc (3×100 mL) The organic layer was washed with water (3×100 mL) dried over sodium sulfate concentrated under reduced pressure The residue was purified by column chromatography (silica gel, 100-200 mesh) eluting with 7% EtOAc in hexane