1-methylpiperidin-3-one

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

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

Procedure: To a solution of 3,5-dimethylisoxazol (4.86 g, 50 mmol) in dry tetrahydrofuran (15 ml) cooled to -78° C was added butyllithium (2.5 M in hexane, 50 mmol). The reaction mixture was stirred for 0.5 h. 1-methyl-piperidin-3-one (2.70 g, 23.9 mmol) dissolved in tetrahydrofuran (25 ml) was added. The reaction mixture was stirred for another 2 h at -78° C. Water (50 ml) was added and the reaction mixture was acidified with concentrated hydrochloric acid. The water phase was extracted with ether (2×50 ml), then made alkaline with potassium carbonate and extracted with methylene chloride (4×50 ml). The combined methylene chloride phases were dried over magnesium sulphate and evaporated giving the title compound in 4.18 g (83%) yield. was added The reaction mixture was stirred for another 2 h at -78° C The water phase was extracted with ether (2×50 ml) extracted with methylene chloride (4×50 ml) The combined methylene chloride phases were dried over magnesium sulphate evaporated

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

Procedure: To a solution of 3,5-dimethylisoxazol (4.86 g, 50 mmol) in dry tetrahydrofuran (15 ml) cooled to -78° C was added butyllithium (2.5 M in hexane, 50 mmol). The reaction mixture was stirred for 0.5 h. 1-methyl-piperidin-3-one (2.70 g, 23.9 mmol) dissolved in tetrahydrofuran (25 ml) was added. The reaction mixture was stirred for another 2 h at -78° C. Water (50 ml) was added and the reaction mixture was acidified with concentrated hydrochloric acid. The water phase was extracted with ether (2×50 ml), then made alkaline with potassium carbonate and extracted with methylene chloride (4×50 ml). The combined methylene chloride phases were dried over magnesium sulphate and evaporated giving the title compound in 4.18 g (83%) yield. was added The reaction mixture was stirred for another 2 h at -78° C The water phase was extracted with ether (2×50 ml) extracted with methylene chloride (4×50 ml) The combined methylene chloride phases were dried over magnesium sulphate evaporated

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

Conditions: temp:-77.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 7.2 ml 2,2,6,6-tetramethylpiperidine (0.034 mol) in 300 ml of dry THF was cooled to -8° C. as 25 ml of 1.6 M butyllithium (0.04 mol) in hexane was added dropwise. The reaction was stirred 20 min then cooled to -77° C. A solution of 2.9 ml of 2-chloropyrazine (0.031 mol) in 5 ml of THF was added dropwise to the reaction. After another 15 min, 3.5 g of 1-methylpiperidin-3-one (0.035 mol) in 10 ml of THF was added dropwise. After the addition, the reaction was stirred 1.5 h followed by addition of a mixture of 8 ml of concentrated HCl and 4 ml of ethanol. The cooling was removed and when the temperature had reached -15° C., 20 ml of 5 N NaOH was added. The volatile organics were evaporated and the aqueous residue was extracted 4 × with 30 ml of CH2Cl2. The extracts were washed with brine, dried and the solvent evaporated to give a brown solid that was dissolved in 300 ml of ether and filtered. The ether was evaporated and the residue recrystallized from hexane to give 3.77 g of (1), 53% yield, mp 111°-112° C. NMR ppm (CDCl3) 1.7-2.2 (5H,m), 2.4 (3H, s), 2.7 (1H, d), 2.85-3.05 (2H, m), 4.4 (1H, bs), 8.35 (1H, d), 8.5 (1H, d). Anal. C10H14ClN3O, requires C: 52.75; H: 6.20; N: 18.46%. Found C: 52.64; H: 6.21; N: 18.21%. was added dropwise After another 15 min After the addition the reaction was stirred 1.5 h The cooling was removed had reached -15° C. 20 ml of 5 N NaOH was added The volatile organics were evaporated the aqueous residue was extracted 4 × with 30 ml of CH2Cl2 The extracts were washed with brine dried the solvent evaporated to give a brown solid that filtered The ether was evaporated the residue recrystallized from hexane

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

Procedure: 26.5 ml of a 2N solution of n-butyllithium in hexane is added dropwise within 30 minutes to a solution of 7.0 g of benzo[b]thiophene in 50 ml of abs. diethyl ether at a reaction temperature of 5° to 10°. The solution is then stirred for a further 1 hour at 0°. There is then added dropwise, in the course of 30 minutes, a solution of 5.9 g of 1-methyl-3-piperidone in 50 ml of abs. diethyl ether, with the reaction temperature being maintained at 0° by external cooling. The reaction solution is stirred for a further 15 hours at room temperature, and is then poured, with stirring, onto 100 g of ice; the aqueous phase is separated, and extracted 3 times with 100 ml of ethyl acetate each time. The combined organic extracts are dried with sodium sulphate, filtered under suction and concentrated by evaporation. The residue is dissolved in 250 ml of 2N hydrochloric acid, and the acid solution is washed with diethyl ether. The aqueous solution is subsequently brought to a pH-value of 12 by the addition of 10 sodium hydroxide solution, and extracted with 500 ml of chloroform. The chloroform solution is dried with sodium sulphate, filtered with suction and concentrated by evaporation to obtain crude 1-methyl-3-(benzo[b]thien-2-yl)-3-piperidinol; the oxalate thereof is prepared, for example, from 1.8 g of free base in ethyl actate and 0.7 g of oxalic acid in 10 ml of ethyl acetate, and it melts at 165°-168° after recrystallisation from ethyl acetate. at a reaction temperature of 5° to 10° There is then added dropwise, in the course of 30 minutes The reaction solution is stirred for a further 15 hours at room temperature is then poured the aqueous phase is separated extracted 3 times with 100 ml of ethyl acetate each time The combined organic extracts are dried with sodium sulphate filtered under suction concentrated by evaporation The residue is dissolved in 250 ml of 2N hydrochloric acid the acid solution is washed with diethyl ether The aqueous solution is subsequently brought to a pH-value of 12 by the addition of 10 sodium hydroxide solution extracted with 500 ml of chloroform The chloroform solution is dried with sodium sulphate filtered with suction concentrated by evaporation

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 400 mg (2.0 mmol) 1-methyl-3,5-dinitro-pyridone, 300 mg 1-methyl-piperidin-3-one and 15 ml 2M ammonia in methanol are heated to 60° C. for 20 h. It is concentrated and purified by chromatography (silica gel, CH2Cl2/MeOH 98/2). It is concentrated purified by chromatography (silica gel, CH2Cl2/MeOH 98/2)

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

Procedure: To a solution of 3,5-dimethylisoxazol (4.86 g, 50 mmol) in dry tetrahydrofuran (15 ml) cooled to -78° C was added butyllithium (2.5 M in hexane, 50 mmol). The reaction mixture was stirred for 0.5 h. 1-methyl-piperidin-3-one (2.70 g, 23.9 mmol) dissolved in tetrahydrofuran (25 ml) was added. The reaction mixture was stirred for another 2 h at -78° C. Water (50 ml) was added and the reaction mixture was acidified with concentrated hydrochloric acid. The water phase was extracted with ether (2×50 ml), then made alkaline with potassium carbonate and extracted with methylene chloride (4×50 ml). The combined methylene chloride phases were dried over magnesium sulphate and evaporated giving the title compound in 4.18 g (83%) yield. was added The reaction mixture was stirred for another 2 h at -78° C The water phase was extracted with ether (2×50 ml) extracted with methylene chloride (4×50 ml) The combined methylene chloride phases were dried over magnesium sulphate evaporated