4-Piperidineacetic acid,1-methyl-,methyl ester

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Methyl diethylphosphonoacetate (88.69 g, 0.422 mol) was added dropwise to a stirred suspension of sodium hydride (18.56 g, 60% dispersion in oil, 0.464 mol) in THF (300 ml) under nitrogen, at such a rate as to maintain the temperature below 30° C. The mixture was stirred for 1 h and a solution of N-methyl-4-piperidinone (47.71 g, 0.422 mol) in THF (150 ml) was added dropwise. The mixture was heated at 60° C. for 4.5 h before removing the solvent under vacuum and redissolving the residue in dichloromethane (300 ml) and water (200 ml). The dichloromethane phase was separated, washed successively with water (200 ml) and saturated sodium bisulphite solution (2×70 ml) and dried (MgSO4). The crude product was chromategraphed on silica gel, eluting with methanol/ether (5:95) to give the title-product (19.75 g, 28%). 1H NMR (250 MHz, CDCl3) δ (3H, s, N-CH3), 2.35 (2H, t, J=6 Hz, CH2), 2.40-2.50 (4H, m, 2 of CH2), 3.00 (2H, t, J=6 Hz, CH2), 3.70 (3H, s, CO2CH3), 5.65 (1H, s, vinyl CH). at such a rate as to maintain the temperature below 30° C before removing the solvent under vacuum redissolving the residue in dichloromethane (300 ml) The dichloromethane phase was separated washed successively with water (200 ml) and saturated sodium bisulphite solution (2×70 ml) dried (MgSO4) eluting with methanol/ether (5:95)

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Methyl diethylphosphonoacetate (88.69 g, 0.422 mol) was added dropwise to a stirred suspension of sodium hydride (18.56 g, 60% dispersion in oil, 0.464 mol) in THF (300 ml) under nitrogen, at such a rate as to maintain the temperature below 30° C. The mixture was stirred for 1 h and a solution of N-methyl-4-piperidinone (47.71 g, 0.422 mol) in THF (150 ml) was added dropwise. The mixture was heated at 60° C. for 4.5 h before removing the solvent under vacuum and redissolving the residue in dichloromethane (300 ml) and water (200 ml). The dichloromethane phase was separated, washed successively with water (200 ml) and saturated sodium bisulphite solution (2×70 ml) and dried (MgSO4). The crude product was chromategraphed on silica gel, eluting with methanol/ether (5:95) to give the title-product (19.75 g, 28%). 1H NMR (250 MHz, CDCl3) δ (3H, s, N-CH3), 2.35 (2H, t, J=6 Hz, CH2), 2.40-2.50 (4H, m, 2 of CH2), 3.00 (2H, t, J=6 Hz, CH2), 3.70 (3H, s, CO2CH3), 5.65 (1H, s, vinyl CH). at such a rate as to maintain the temperature below 30° C before removing the solvent under vacuum redissolving the residue in dichloromethane (300 ml) The dichloromethane phase was separated washed successively with water (200 ml) and saturated sodium bisulphite solution (2×70 ml) dried (MgSO4) eluting with methanol/ether (5:95)

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

実験手順: LAH (2.25 g, 59.3 mmol) was slowly added to 150 mL of THF. (1-Methyl-piperidin-4-yl)-acetic acid methyl ester (Step B) in 30 mL of THF was added dropwise to the LAH in THF and the resulting mixture was stirred for 4 h. Water (2.26 mL), 2.26 mL of 15% NaOH and 6.78 mL of water were carefully added and stirring was continued for 30 min. The mixture was filtered through Celite®, the solids were washed with EtOAc and the filtrate was evaporated, giving 2-(1-methyl-piperidin-4-yl)-ethanol as a yellow oil. stirring was continued for 30 min The mixture was filtered through Celite® the solids were washed with EtOAc the filtrate was evaporated

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

実験手順: (1-Methyl-piperidin-4-ylidene)-acetic acid methyl ester (Step A) was stirred under H2 overnight (1.1 g of 10% Pd/C and 200 mL EtOH), filtered and evaporated to give (1-methyl-piperidin-4-yl)-acetic acid methyl ester as a yellow oil/white solid. filtered evaporated

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

実験手順: (1-Methyl-piperidin-4-ylidene)-acetic acid methyl ester (Step A) was stirred under H2 overnight (1.1 g of 10% Pd/C and 200 mL EtOH), filtered and evaporated to give (1-methyl-piperidin-4-yl)-acetic acid methyl ester as a yellow oil/white solid. filtered evaporated

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Methyl diethylphosphonoacetate (88.69 g, 0.422 mol) was added dropwise to a stirred suspension of sodium hydride (18.56 g, 60% dispersion in oil, 0.464 mol) in THF (300 ml) under nitrogen, at such a rate as to maintain the temperature below 30° C. The mixture was stirred for 1 h and a solution of N-methyl-4-piperidinone (47.71 g, 0.422 mol) in THF (150 ml) was added dropwise. The mixture was heated at 60° C. for 4.5 h before removing the solvent under vacuum and redissolving the residue in dichloromethane (300 ml) and water (200 ml). The dichloromethane phase was separated, washed successively with water (200 ml) and saturated sodium bisulphite solution (2×70 ml) and dried (MgSO4). The crude product was chromategraphed on silica gel, eluting with methanol/ether (5:95) to give the title-product (19.75 g, 28%). 1H NMR (250 MHz, CDCl3) δ (3H, s, N-CH3), 2.35 (2H, t, J=6 Hz, CH2), 2.40-2.50 (4H, m, 2 of CH2), 3.00 (2H, t, J=6 Hz, CH2), 3.70 (3H, s, CO2CH3), 5.65 (1H, s, vinyl CH). at such a rate as to maintain the temperature below 30° C before removing the solvent under vacuum redissolving the residue in dichloromethane (300 ml) The dichloromethane phase was separated washed successively with water (200 ml) and saturated sodium bisulphite solution (2×70 ml) dried (MgSO4) eluting with methanol/ether (5:95)

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

実験手順: LAH (2.25 g, 59.3 mmol) was slowly added to 150 mL of THF. (1-Methyl-piperidin-4-yl)-acetic acid methyl ester (Step B) in 30 mL of THF was added dropwise to the LAH in THF and the resulting mixture was stirred for 4 h. Water (2.26 mL), 2.26 mL of 15% NaOH and 6.78 mL of water were carefully added and stirring was continued for 30 min. The mixture was filtered through Celite®, the solids were washed with EtOAc and the filtrate was evaporated, giving 2-(1-methyl-piperidin-4-yl)-ethanol as a yellow oil. stirring was continued for 30 min The mixture was filtered through Celite® the solids were washed with EtOAc the filtrate was evaporated

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

実験手順: (1-Methyl-piperidin-4-ylidene)-acetic acid methyl ester (Step A) was stirred under H2 overnight (1.1 g of 10% Pd/C and 200 mL EtOH), filtered and evaporated to give (1-methyl-piperidin-4-yl)-acetic acid methyl ester as a yellow oil/white solid. filtered evaporated