3-morpholin-4-yl-3-oxopropanenitrile

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A nitrogen inerted reactor is charged with 5% Pt-C (43 g; 58% water-wet) followed by 3-morpholin-4-yl-3-oxo-propionitrile (2.8 mol). A solution of MeOH (3.4 L) and 12N HCl (3.08 mol) is added at such a rate as to maintain an internal temperature of ca. 25° C. The vessel and its contents are degassed via three N2 pressure purges (50 psi). The atmosphere is switched to hydrogen via three H2 pressure purges (50 psi), and the reaction is stirred vigorously at ca. 25° C. under a sustained pressure of hydrogen (50 psi) for ca. 24 hours. The H2 pressure is released and replaced with N2. The reaction is passed through filter agent, which is subsequently washed with MeOH (500 mL). The reaction is concentrated in vacuo to a volume of ca. 1.4 L, and IPA (2.2 L) is added. The reaction mixture is cooled to 0° C. and filtered. The filter cake is washed with MtBE (500 mL) and dried under vacuum at ca. 30° C. to provide 3-amino-1-morpholin-4-yl-propan-1-one, hydrochloride as a white solid (439 g). This material is used in subsequent steps without further purification. The vessel and its contents are degassed via three N2 pressure through filter agent, which is subsequently washed with MeOH (500 mL) The reaction is concentrated in vacuo to a volume of ca. 1.4 L, and IPA (2.2 L) is added The reaction mixture is cooled to 0° C. filtered The filter cake is washed with MtBE (500 mL) dried under vacuum at ca. 30° C.

反応条件: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A nitrogen inerted reactor equipped with reflux condenser, nitrogen inlet and mechanical stirring is charged with morpholine (1.2 mol), methyl cyanoacetate (1.0 mol) and MtBE (52 mL). The homogeneous solution is heated to ca. 55° C. and stirred at that temperature for 12 to 18 hours. MtBE (33 mL) is added over ca. 15 minutes, and the solution is slowly cooled below 50° C. where nucleation becomes evident. Additional MTBE (66 μL) is added over a 1-hour period. During this time, the reaction is allowed to cool to near ambient temperature. After complete MtBE addition, the reaction is cooled with stirring to ca. 0° C. The resulting precipitate is collected via filtration and the cake is washed with additional MtBE (ca. 40 mL). The solid is dried under vacuum at ca. 45° C. to provide 3-morpholin-4-yl-3-oxo-propionitrile (139 g). This material is used in subsequent steps without further purification. A nitrogen inerted reactor equipped with reflux condenser, nitrogen inlet stirred at that temperature for 12 to 18 hours MtBE (33 mL) is added over ca. 15 minutes is slowly cooled below 50° C. to cool to near ambient temperature After complete MtBE addition the reaction is cooled with stirring to ca. 0° C The resulting precipitate is collected via filtration the cake is washed with additional MtBE (ca. 40 mL) The solid is dried under vacuum at ca. 45° C.

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A nitrogen inerted reactor is charged with 5% Pt—C (43 g; 58% water-wet) followed by 3-morpholin-4-yl-3-oxo-propionitrile (2.8 mol). A solution of MeOH (3.4 L) and 12N HCl (3.08 mol) is added at such a rate as to maintain an internal temperature of ca. 25° C. The vessel and its contents are degassed via three N2 pressure purges (50 psi). The atmosphere is switched to hydrogen via three H2 pressure purges (50 psi), and the reaction is stirred vigorously at ca. 25° C. under a sustained pressure of hydrogen (50 psi) for ca. 24 hours. The H2 pressure is released and replaced with N2. The reaction is passed through filter agent, which is subsequently washed with MeOH (500 mL). The reaction is concentrated in vacuo to a volume of ca. 1.4 L, and IPA (2.2 L) is added. The reaction mixture is cooled to 0° C. and filtered. The filter cake is washed with MtBE (500 mL) and dried under vacuum at ca. 30C to provide 3-amino-1-morpholin-4-yl-propan-1-one, hydrochloride as a white solid (439 g). This material is used in subsequent steps without further purification. The vessel and its contents are degassed via three N2 pressure through filter agent, which is subsequently washed with MeOH (500 mL) The reaction is concentrated in vacuo to a volume of ca. 1.4 L, and IPA (2.2 L) is added The reaction mixture is cooled to 0° C. filtered The filter cake is washed with MtBE (500 mL) dried under vacuum at ca. 30C

反応条件: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A nitrogen inerted reactor equipped with reflux condenser, nitrogen inlet and mechanical stirring is charged with morpholine (1.2 mol), methyl cyanoacetate (1.0 mol) and MtBE (52 mL). The homogeneous solution is heated to ca. 55° C. and stirred at that temperature for 12 to 18 hours. MtBE (33 mL) is added over ca. 15 minutes, and the solution is slowly cooled below 50° C. where nucleation becomes evident. Additional MtBE (66 mL) is added over a 1-hour period. During this time, the reaction is allowed to cool to near ambient temperature. After complete MtBE addition, the reaction is cooled with stirring to ca. 0° C. The resulting precipitate is collected via filtration and the cake is washed with additional MtBE (ca. 40 mL). The solid is dried under vacuum at ca. 45° C. to provide 3-morpholin-4-yl-3-oxo-propionitrile (139 g). This material is used in subsequent steps without further purification. A nitrogen inerted reactor equipped with reflux condenser, nitrogen inlet stirred at that temperature for 12 to 18 hours MtBE (33 mL) is added over ca. 15 minutes is slowly cooled below 50° C. Additional MtBE (66 mL) is added over a 1-hour period to cool to near ambient temperature After complete MtBE addition the reaction is cooled with stirring to ca. 0° C The resulting precipitate is collected via filtration the cake is washed with additional MtBE (ca. 40 mL) The solid is dried under vacuum at ca. 45° C.

反応条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A nitrogen inerted reactor is charged with 5% Pt—C (43 g; 58% water-wet) followed by 3-morpholin-4-yl-3-oxo-propionitrile (2.8 mol). A solution of MeOH (3.4 L) and 12N HCl (3.08 mol) is added at such a rate as to maintain an internal temperature of ca. 25° C. The vessel and its contents are degassed via three N2 pressure purges (50 psi). The atmosphere is switched to hydrogen via three H2 pressure purges (50 psi), and the reaction is stirred vigorously at ca. 25° C. under a sustained pressure of hydrogen (50 psi) for ca. 24 hours. The H2 pressure is released and replaced with N2. The reaction is passed through filter agent, which is subsequently washed with MeOH (500 mL). The reaction is concentrated in vacuo to a volume of ca. 1.4 L, and IPA (2.2 L) is added. The reaction mixture is cooled to 0° C. and filtered. The filter cake is washed with MtBE (500 mL) and dried under vacuum at ca. 30° C. to provide 3-amino-1-morpholin-4-yl-propan-1-one, hydrochloride as a white solid (439 g). This material is used in subsequent steps without further purification. The vessel and its contents are degassed via three N2 pressure through filter agent, which is subsequently washed with MeOH (500 mL) The reaction is concentrated in vacuo to a volume of ca. 1.4 L, and IPA (2.2 L) is added The reaction mixture is cooled to 0° C. filtered The filter cake is washed with MtBE (500 mL) dried under vacuum at ca. 30° C.

反応条件: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A nitrogen inerted reactor equipped with reflux condenser, nitrogen inlet and mechanical stirring is charged with morpholine (1.2 mol), methyl cyanoacetate (1.0 mol) and MtBE (52 mL). The homogeneous solution is heated to ca. 55° C. and stirred at that temperature for 12 to 18 hours. MtBE (33 mL) is added over ca. 15 minutes, and the solution is slowly cooled below 50° C. where nucleation becomes evident. Additional MtBE (66 mL) is added over a 1-hour period. During this time, the reaction is allowed to cool to near ambient temperature. After complete MtBE addition, the reaction is cooled with stirring to ca. 0° C. The resulting precipitate is collected via filtration and the cake is washed with additional MtBE (ca. 40 mL). The solid is dried under vacuum at ca. 45° C. to provide 3-morpholin-4-yl-3-oxo-propionitrile (139 g). This material is used in subsequent steps without further purification. A nitrogen inerted reactor equipped with reflux condenser, nitrogen inlet stirred at that temperature for 12 to 18 hours MtBE (33 mL) is added over ca. 15 minutes is slowly cooled below 50° C. Additional MtBE (66 mL) is added over a 1-hour period to cool to near ambient temperature After complete MtBE addition the reaction is cooled with stirring to ca. 0° C The resulting precipitate is collected via filtration the cake is washed with additional MtBE (ca. 40 mL) The solid is dried under vacuum at ca. 45° C.

反応条件: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A nitrogen inerted reactor equipped with reflux condenser, nitrogen inlet and mechanical stirring is charged with morpholine (1.2 mol), methyl cyanoacetate (1.0 mol) and MtBE (52 mL). The homogeneous solution is heated to ca. 55° C. and stirred at that temperature for 12 to 18 hours. MtBE (33 mL) is added over ca. 15 minutes, and the solution is slowly cooled below 50° C. where nucleation becomes evident. Additional MtBE (66 mL) is added over a 1-hour period. During this time, the reaction is allowed to cool to near ambient temperature. After complete MtBE addition, the reaction is cooled with stirring to ca. 0° C. The resulting precipitate is collected via filtration and the cake is washed with additional MtBE (ca. 40 mL). The solid is dried under vacuum at ca. 45° C. to provide 3-morpholin-4-yl-3-oxo-propionitrile (139 g). This material is used in subsequent steps without further purification. A nitrogen inerted reactor equipped with reflux condenser, nitrogen inlet stirred at that temperature for 12 to 18 hours MtBE (33 mL) is added over ca. 15 minutes is slowly cooled below 50° C. Additional MtBE (66 mL) is added over a 1-hour period to cool to near ambient temperature After complete MtBE addition the reaction is cooled with stirring to ca. 0° C The resulting precipitate is collected via filtration the cake is washed with additional MtBE (ca. 40 mL) The solid is dried under vacuum at ca. 45° C.