3-methoxypropanenitrile

Conditions: temp:3.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a three-necked reaction vessel equipped with stirrer, gas delivery tube, thermometer and reflux condenser is charged 85.1 parts of 3-methoxypropionitrile, 32.0 parts of reagent grade methanol and 300 parts of toluene. The exit from the reflux condenser is connected to a drying tower filled with a commercially available drying agent and a bath is provided for cooling the vessel below 0° C. Hydrochloric acid gas flow is controlled by means of a rotameter and is passed through a calcium chloride filled trap which serves both as a means for drying the gas and as a receiver in case liquid is sucked back into the line. After charging the reagents and toluene, the solution is stirred and cooled to 3° C. and the HCl gas is then fed, while controlling the temperature to -4° to 1° C., until 38.0 parts have been added. The HCl gas is added as rapidly as possible commensurate with complete adsorption and good temperature control. The mixture is then stirred for 15 hours in an ice bath (maximum 10° C.). Crystals of methyl-3-methoxypropionimidate hydrochloride appear 2.25 hours after the HCl addition is complete. 46.5 Hours after the HCl addition is stopped, an 80% yield of methyl-3-methoxypropionimidate hydrochloride is formed. To a three-necked reaction vessel equipped with stirrer, gas delivery tube thermometer and reflux condenser filled with a commercially available drying agent a bath is provided for cooling the vessel below 0° C is passed through a calcium chloride filled trap for drying the gas to -4° to 1° C. until 38.0 parts have been added The HCl gas is added as rapidly as possible commensurate with complete adsorption and good temperature control The mixture is then stirred for 15 hours in an ice bath (maximum 10° C.) after the HCl addition 46.5 Hours after the HCl addition

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

Procedure: 68 g (0.8 mol) of 3-methoxypropionitrile were dissolved in 1000 mL THF freshly distilled over LiAlH4 and treated with 150.3 g (2.2 mol) Zn/Cu pair under inert gas. With moderate reflux 267.2 g (1.6 mol) of 2-bromoacetic acid ethyl ester were added drop-by-drop to the vigorously stirred suspension within 75 minutes. After the reaction had started, the heat was turned off and the slight reflux adjusted via the drop velocity. To complete the reaction, the solution was stirred for 30 minutes at the boiling temperature of THF. Then, 420 mL of 10% HCl were added drop-by-drop within 30 minutes at 15° C. and stirred for another 30 minutes. The solution was filtered from the non-converted zinc and the filtrate was extracted three times with 300 mL of CHCl3 each. The organic phases were washed four times with water and once with 5% NAHCO3 solution and the solvent was removed following drying over MGSO4 under vacuum. The obtained reddish liquid was distilled under oil pump vacuum. The fraction at 85° C./0.5 torr yielded 106.8 g (0.62 mol) of 5-methoxy-3-oxopentanic acid ethyl ester as a colorless, fruity smelling oil with a refractive index nD22 =1.434. The yield was to 77.5% based on 3-methoxypropionitrile. freshly distilled over LiAlH4 were added drop-by-drop to the vigorously stirred suspension within 75 minutes the slight reflux the reaction The solution was filtered from the non-converted zinc the filtrate was extracted three times with 300 mL of CHCl3 each The organic phases were washed four times with water once with 5% NAHCO3 solution and the solvent was removed following drying over MGSO4 under vacuum The obtained reddish liquid was distilled under oil pump vacuum

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

Procedure: 68 g (0.8 mol) of 3-methoxypropionitrile were dissolved in 1000 mL THF freshly distilled over LiAlH4 and treated with 150.3 g (2.2 mol) Zn/Cu pair under inert gas. With moderate reflux 267.2 g (1.6 mol) of 2-bromoacetic acid ethyl ester were added drop-by-drop to the vigorously stirred suspension within 75 minutes. After the reaction had started, the heat was turned off and the slight reflux adjusted via the drop velocity. To complete the reaction, the solution was stirred for 30 minutes at the boiling temperature of THF. Then, 420 mL of 10% HCl were added drop-by-drop within 30 minutes at 15° C. and stirred for another 30 minutes. The solution was filtered from the non-converted zinc and the filtrate was extracted three times with 300 mL of CHCl3 each. The organic phases were washed four times with water and once with 5% NAHCO3 solution and the solvent was removed following drying over MGSO4 under vacuum. The obtained reddish liquid was distilled under oil pump vacuum. The fraction at 85° C./0.5 torr yielded 106.8 g (0.62 mol) of 5-methoxy-3-oxopentanic acid ethyl ester as a colorless, fruity smelling oil with a refractive index nD22 =1.434. The yield was to 77.5% based on 3-methoxypropionitrile. freshly distilled over LiAlH4 were added drop-by-drop to the vigorously stirred suspension within 75 minutes the slight reflux the reaction The solution was filtered from the non-converted zinc the filtrate was extracted three times with 300 mL of CHCl3 each The organic phases were washed four times with water once with 5% NAHCO3 solution and the solvent was removed following drying over MGSO4 under vacuum The obtained reddish liquid was distilled under oil pump vacuum

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

Procedure: 3-Methoxypropanenitrile (5.0 g, 58.8 mmol) was dissolved in anhydrous ethanol (50 mL) under an atmosphere of Ar. The solution was cooled to 0° C., saturated with HCl gas, stirred for 6 h, allowed to warm to RT, and stirred for 6 h. The solvent was removed in vacuo. The residue was slurried with hexanes (50 mL) and sonicated for 10 min. The solids were allowed to settle and the solvent was removed by decantation. This was repeated (3×). The solid was collected and dried under high vacuum for 5 h to afford ethyl 3-methoxypropanimidate hydrochloride (6.2 g, 63%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 12.03 (br s, 1H), 11.22 (br s, 1H), 4.42 (q, J=7.0 Hz, 2H), 3.60 (t, J=5.9 Hz, 2H), 3.23 (s, 3H), 2.87 (t, J=5.9 Hz, 2H), 1.33 (t, J=7.0 Hz, 3H). stirred for 6 h The solvent was removed in vacuo sonicated for 10 min the solvent was removed by decantation The solid was collected dried under high vacuum for 5 h

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

Procedure: 3-Methoxypropanenitrile (5.0 g, 58.8 mmol) was dissolved in anhydrous ethanol (50 mL) under an atmosphere of Ar. The solution was cooled to 0° C., saturated with HCl gas, stirred for 6 h, allowed to warm to RT, and stirred for 6 h. The solvent was removed in vacuo. The residue was slurried with hexanes (50 mL) and sonicated for 10 min. The solids were allowed to settle and the solvent was removed by decantation. This was repeated (3×). The solid was collected and dried under high vacuum for 5 h to afford ethyl 3-methoxypropanimidate hydrochloride (6.2 g, 63%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 12.03 (br s, 1H), 11.22 (br s, 1H), 4.42 (q, J=7.0 Hz, 2H), 3.60 (t, J=5.9 Hz, 2H), 3.23 (s, 3H), 2.87 (t, J=5.9 Hz, 2H), 1.33 (t, J=7.0 Hz, 3H). stirred for 6 h The solvent was removed in vacuo sonicated for 10 min the solvent was removed by decantation The solid was collected dried under high vacuum for 5 h

Conditions: temp:3.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 3-necked reaction vessel equipped with stirrer, gas delivery tube, thermometer and reflux condenser is charged 85.1 parts of 3-methoxypropionitrile, 32.0 parts of reagent grade methanol and 300 parts of toluene. The exit from the reflux condenser is connected to a drying tower filled with a commercially available drying agent and a bath is provided for cooling the vessel below 0° C. Hydrochloric acid gas flow is controlled by means of a rotameter and is passed through a calcium chloride filled trap which serves both as a means for drying the gas and as a receiver in case liquid is sucked back into the line. After charging the reagents and toluene, the solution is stirred and cooled to 3° C. and the HCl gas is then fed, while controlling the temperature to -4° to 1° C., until 38.0 parts have been added. The HCl gas is added as rapidly as possible commensurate with complete adsorption and good temperature control. The mixture is then stirred for 15 hours in an ice bath (maximum 10° C.). Crystals of methyl-3-methoxypropionimidate hydrochloride appear 2.25 hours after the HCl addition is complete. 46.5 Hours after the HCl addition is stopped, an 80% yield of methyl-3-methoxypropionimidate hydrochloride is formed. To a 3-necked reaction vessel equipped with stirrer, gas delivery tube thermometer and reflux condenser filled with a commercially available drying agent a bath is provided for cooling the vessel below 0° C is passed through a calcium chloride filled trap for drying the gas to -4° to 1° C. until 38.0 parts have been added The HCl gas is added as rapidly as possible commensurate with complete adsorption and good temperature control The mixture is then stirred for 15 hours in an ice bath (maximum 10° C.) after the HCl addition 46.5 Hours after the HCl addition

Conditions: temp:3.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 3-necked reaction vessel equipped with stirrer, gas delivery tube, thermometer and reflux condenser is charged 85.1 parts of 3-methoxypropionitrile, 32.0 parts of reagent grade methanol and 300 parts of toluene. The exit from the reflux condenser is connected to a drying tower filled with a commercially available drying agent and a bath is provided for cooling the vessel below 0° C. Hydrochloric acid gas flow is controlled by means of a rotameter and is passed through a calcium chloride filled trap which serves both as a means for drying the gas and as a receiver in case liquid is sucked back into the line. After charging the reagents and toluene, the solution is stirred and cooled to 3° C. and the HCl gas is then fed, while controlling the temperature to -4 to 1° C., until 38.0 parts have been added. The HCl gas is added as rapidly as possible commensurate with complete adsorption and good temperature control. The mixture is then stirred for 15 hours in an ice bath (maximum 10° C.). Crystals of methyl-3-methoxypropionimidate hydrochloride appear 2.25 hours after the HCl addition is complete. 46.5 Hours after the HCl addition is stopped, an 80% yield of methyl-3-methoxypropionimidate hydrochloride is formed. To a 3-necked reaction vessel equipped with stirrer, gas delivery tube thermometer and reflux condenser filled with a commercially available drying agent a bath is provided for cooling the vessel below 0° C is passed through a calcium chloride filled trap for drying the gas to -4 to 1° C. until 38.0 parts have been added The HCl gas is added as rapidly as possible commensurate with complete adsorption and good temperature control The mixture is then stirred for 15 hours in an ice bath (maximum 10° C.) after the HCl addition 46.5 Hours after the HCl addition

Conditions: temp:3.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a three-necked reaction vessel equipped with stirrer, gas delivery tube, thermometer and reflux condenser is charged 85.1 parts of 3-methoxypropionitrile, 32.0 parts of reagent grade methanol and 300 parts of toluene. The exit from the reflux condenser is connected to a drying tower filled with a commercially available drying agent and a bath is provided for cooling the vessel below 0° C. Hydrochloric acid gas flow is controlled by means of a rotameter and is passed through a calcium chloride filled trap which serves both as a means for drying the gas and as a receiver in case liquid is sucked back into the line. After charging the reagents and toluene, the solution is stirred and cooled to 3° C. and the HCl gas is then fed, while controlling the temperature to -4° to 1° C., until 38.0 parts have been added. The HCl gas is added as rapidly as possible commensurate with complete adsorption and good temperature control. The mixture is then stirred for 15 hours in an ice bath (maximum 10° C.). Crystals of methyl-3-methoxypropionimidate hydrochloride appear 2.25 hours after the HCl addition is complete. 46.5 Hours after the HCl addition is stopped, an 80% yield of methyl-3-methoxypropionimidate hydrochloride is formed. To a three-necked reaction vessel equipped with stirrer, gas delivery tube thermometer and reflux condenser filled with a commercially available drying agent a bath is provided for cooling the vessel below 0° C is passed through a calcium chloride filled trap for drying the gas to -4° to 1° C. until 38.0 parts have been added The HCl gas is added as rapidly as possible commensurate with complete adsorption and good temperature control The mixture is then stirred for 15 hours in an ice bath (maximum 10° C.) after the HCl addition 46.5 Hours after the HCl addition

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

Procedure: 68 g (0.8 mol) of 3-methoxypropionitrile were dissolved in 1000 mL THF freshly distilled over LiAlH4 and treated with 150.3 g (2.2 mol) Zn/Cu pair under inert gas. With moderate reflux 267.2 g (1.6 mol) of 2-bromoacetic acid ethyl ester were added drop-by-drop to the vigorously stirred suspension within 75 minutes. After the reaction had started, the heat was turned off and the slight reflux adjusted via the drop velocity. To complete the reaction, the solution was stirred for 30 minutes at the boiling temperature of THF. Then, 420 mL of 10% HCl were added drop-by-drop within 30 minutes at 15° C. and stirred for another 30 minutes. The solution was filtered from the non-converted zinc and the filtrate was extracted three times with 300 mL of CHCl3 each. The organic phases were washed four times with water and once with 5% NAHCO3 solution and the solvent was removed following drying over MGSO4 under vacuum. The obtained reddish liquid was distilled under oil pump vacuum. The fraction at 85° C./0.5 torr yielded 106.8 g (0.62 mol) of 5-methoxy-3-oxopentanic acid ethyl ester as a colorless, fruity smelling oil with a refractive index nD22 =1.434. The yield was to 77.5% based on 3-methoxypropionitrile. freshly distilled over LiAlH4 were added drop-by-drop to the vigorously stirred suspension within 75 minutes the slight reflux the reaction The solution was filtered from the non-converted zinc the filtrate was extracted three times with 300 mL of CHCl3 each The organic phases were washed four times with water once with 5% NAHCO3 solution and the solvent was removed following drying over MGSO4 under vacuum The obtained reddish liquid was distilled under oil pump vacuum

Conditions: temp:3.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 3-necked reaction vessel equipped with stirrer, gas delivery tube, thermometer and reflux condenser is charged 85.1 parts of 3-methoxypropionitrile, 32.0 parts of reagent grade methanol and 300 parts of toluene. The exit from the reflux condenser is connected to a drying tower filled with a commercially available drying agent and a bath is provided for cooling the vessel below 0° C. Hydrochloric acid gas flow is controlled by means of a rotameter and is passed through a calcium chloride filled trap which serves both as a means for drying the gas and as a receiver in case liquid is sucked back into the line. After charging the reagents and toluene, the solution is stirred and cooled to 3° C. and the HCl gas is then fed, while controlling the temperature to -4° to 1° C., until 38.0 parts have been added. The HCl gas is added as rapidly as possible commensurate with complete adsorption and good temperature control. The mixture is then stirred for 15 hours in an ice bath (maximum 10° C.). Crystals of methyl-3-methoxypropionimidate hydrochloride appear 2.25 hours after the HCl addition is complete. 46.5 Hours after the HCl addition is stopped, an 80% yield of methyl-3-methoxypropionimidate hydrochloride is formed. To a 3-necked reaction vessel equipped with stirrer, gas delivery tube thermometer and reflux condenser filled with a commercially available drying agent a bath is provided for cooling the vessel below 0° C is passed through a calcium chloride filled trap for drying the gas to -4° to 1° C. until 38.0 parts have been added The HCl gas is added as rapidly as possible commensurate with complete adsorption and good temperature control The mixture is then stirred for 15 hours in an ice bath (maximum 10° C.) after the HCl addition 46.5 Hours after the HCl addition

Conditions: temp:30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 200 g (1.20 mole) of 3,4-dimethoxy-benzaldehyde, 150 g (1.75 mole) of β-methoxy-propinitrile, 260 ml of methanol and 10 g of a 55% methanolic potassium hydroxide solution is stirred at 60°-62° C. for 8 hours, whereupon the reaction mixture is cooled to 30° C., and 170 g of a 55% methanolic potassium hydroxide solution are added dropwise. The reaction mixture is stirred for 5 hours and diluted with 1000 ml of water. The precipitated crystalline product is filtered, washed with methanol and water. Thus 280 g of α-(3,4-dimethoxy-benzal)-β-methoxy-propionitrile are obtained, yield 85%, mp.: 82°-83° C. The reaction mixture is stirred for 5 hours The precipitated crystalline product is filtered washed with methanol and water

Conditions: temp:30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 200 g (1.20 mole) of 3,4-dimethoxy-benzaldehyde, 150 g (1.75 mole) of β-methoxy-propinitrile, 260 ml of methanol and 10 g of a 55% methanolic potassium hydroxide solution is stirred at 60°-62° C. for 8 hours, whereupon the reaction mixture is cooled to 30° C., and 170 g of a 55% methanolic potassium hydroxide solution are added dropwise. The reaction mixture is stirred for 5 hours and diluted with 1000 ml of water. The precipitated crystalline product is filtered, washed with methanol and water. Thus 280 g of α-(3,4-dimethoxy-benzal)-β-methoxy-propionitrile are obtained, yield 85%, mp.: 82°-83° C. The reaction mixture is stirred for 5 hours The precipitated crystalline product is filtered washed with methanol and water