Chloroacetyl chloride → 1,1-Dimethylethyl 4-(3-oxo-4-morpholinyl)-1-piperidinecarboxylate

Temperature

0 °C

tert-Butyl 4-(2-hydroxyethyl)amino-1-piperidinecarboxylate (2.4 g) obtained in Example 91a) and triethylamine (1.0 g) were dissolved in THF (70 ml). While the mixture was cooled to 0° C., chloroacetyl chloride (0.72 ml) was added dropwise thereto, and mixed at 0° C. for 2 hours. Sodium hydride (60%; 1.0 g) and DMF (30 ml) were added to the reaction mixture, and mixed at 80° C. for 15 hours. The reaction mixture was concentrated under reduced pressure, water was added thereto, and then extracted with ethyl acetate. The extract was washed with water, a 5% aqueous citric acid solution and saturated brine and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the residue was purified with silica gel column (ethyl acetate/hexane=1/1 to ethyl acetate) to obtain the title compound as a colorless oil (0.51 g, 18%).

1. additionmixed at 0° C. for 2 hours
2. additionmixed at 80° C. for 15 hours
3. concentrationThe reaction mixture was concentrated under reduced pressure, water
4. additionwas added
5. extractionextracted with ethyl acetate
6. washThe extract was washed with water
7. dry with materiala 5% aqueous citric acid solution and saturated brine and dried over anhydrous sodium sulfate
8. distillationThe solvent was distilled off under reduced pressure
9. customthe residue was purified with silica gel column (ethyl acetate/hexane=1/1 to ethyl acetate)

ORD record

ord-b818c237a90b4455a29538009a52e70c

Source dataset

uspto-grants-2010_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07820673B2