Morpholine → 3-morpholin-4-ylbenzonitrile

Temperature

-10 °C

3-Cyanophenol (1.77 g, 14.9mmol) and triethylamine (6.30 ml, 45.2 mmol) were dissolved in methylene chloride (75 ml) and stirred at -10° C. in an argon gas atmosphere. A solution of trifluoroacetic anhydride (3.79 ml, 22.5 mmol) dissolved in methylene chloride (15 ml) was added dropwise thereto, and after the addition was completed, the mixture was stirred for 1.5 hours. After the reaction was completed, the solvent was removed under reduced pressure, and an aqueous solution of sodium hydrogen carbonate was added to the resulting concentrated residue and the mixture was extracted with methylene chloride. The organic layer was washed with a saturated aqueous sodium chloride solution and dried over sodium sulfate. The drying agent was filtered off and the filtrate was concentrated. The resulting concentrated residue was purified by silica gel column chromatography (chloroform/methanol=100) to give oily substances. The resulting oily substances were dissolved in acetonitrile (40 ml). Morpholine (33.0 ml, 378 mmol) was added thereto and the mixture was stirred for 3 days under heating at reflux. The solvent and unreacted reagents were distilled off under reduced pressure, water was added to the concentrated residue, and the mixture was extracted with chloroform. The organic layer was dried (over sodium sulfate), the drying agent was filtered off, and the filtrate was concentrated. The resulting concentrated filtrate was purified by silica gel column chromatography (eluent: chloroform/hexane=1/2) to give the title compound (0.74 g, 26%) as oily substances.

1. additionwas added dropwise
2. additionafter the addition
3. stirringthe mixture was stirred for 1.5 hours
4. customthe solvent was removed under reduced pressure
5. additionan aqueous solution of sodium hydrogen carbonate was added to the resulting concentrated residue
6. extractionthe mixture was extracted with methylene chloride
7. washThe organic layer was washed with a saturated aqueous sodium chloride solution
8. dry with materialdried over sodium sulfate
9. filtrationThe drying agent was filtered off
10. concentrationthe filtrate was concentrated
11. customThe resulting concentrated residue was purified by silica gel column chromatography (chloroform/methanol=100)
12. customto give oily substances
13. stirringthe mixture was stirred for 3 days
14. temperatureunder heating
15. temperatureat reflux
16. distillationThe solvent and unreacted reagents were distilled off under reduced pressure, water
17. additionwas added to the concentrated residue
18. extractionthe mixture was extracted with chloroform
19. dry with materialThe organic layer was dried (over sodium sulfate)
20. filtrationthe drying agent was filtered off
21. concentrationthe filtrate was concentrated
22. customThe resulting concentrated filtrate was purified by silica gel column chromatography (eluent: chloroform/hexane=1/2)

ORD record

ord-7334e60abfb642fa858baf68c48b2a52

Source dataset

uspto-grants-2000_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06127541