Methyl cyanoacetate → 4-(Cyanoacetyl)morpholine

Temperature

55 °C

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.

1. customA nitrogen inerted reactor equipped
2. temperaturewith reflux condenser, nitrogen inlet
3. stirringstirred at that temperature for 12 to 18 hours
4. additionMtBE (33 mL) is added over ca. 15 minutes
5. customis slowly cooled below 50° C.
6. additionAdditional MtBE (66 mL) is added over a 1-hour period
7. temperatureto cool to near ambient temperature
8. additionAfter complete MtBE addition
9. temperaturethe reaction is cooled
10. stirringwith stirring to ca. 0° C
11. filtrationThe resulting precipitate is collected via filtration
12. washthe cake is washed with additional MtBE (ca. 40 mL)
13. customThe solid is dried under vacuum at ca. 45° C.

ORD record

ord-48544af593624fdc8e0c1bba3e80d9c7

Source dataset

uspto-grants-2008_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07399773B2