Potassium Carbonate → 1-[3-(Trifluoromethyl)pyridin-2-yl]piperidin-4-one

Temperature

100 °C

2-Chloro-3-(trifluoromethyl)pyridine (11.92 g, 65.7 mmol)), K2CO3(19.10 g, 138 mmol), and 1,4-dioxa-8-azaspiro[4.5]decane (8.85 mL, 69.0 mmol) were combined in DMSO (65 mL) and stirred at 100° C. for 3 hours. The mixture was treated with additional 1,4-dioxa-8-azaspiro[4.5]decane (2.0 mL, 16 mmol), stirred for 2 hours, treated with additional 1,4-dioxa-8-azaspiro[4.5]decane (1.0 mL, 7.8 mmol), and stirred for 1 hour. The mixture was diluted with diethyl ether (200 mL), washed with water (250 mL), washed with brine (100 mL), dried (Na2SO4), filtered, and the filtrate was concentrated under reduced pressure. The residue was dissolved in concentrated HCl (25 mL), stirred for 3 hours, basified with concentrated NH4OH, extracted with CH2Cl2, and the phases separated. The organic phase was dried (Na2SO4), filtered, and the filtrate concentrated under reduced pressure. The residue was purified via flash chromatography (20% to 40% diethyl ether/hexanes) to provide the title compound.

1. stirringstirred for 2 hours
2. stirringstirred for 1 hour
3. washwashed with water (250 mL)
4. washwashed with brine (100 mL)
5. dry with materialdried (Na2SO4)
6. filtrationfiltered
7. concentrationthe filtrate was concentrated under reduced pressure
8. dissolutionThe residue was dissolved in concentrated HCl (25 mL)
9. stirringstirred for 3 hours
10. extractionextracted with CH2Cl2
11. customthe phases separated
12. dry with materialThe organic phase was dried (Na2SO4)
13. filtrationfiltered
14. concentrationthe filtrate concentrated under reduced pressure
15. customThe residue was purified via flash chromatography (20% to 40% diethyl ether/hexanes)

ORD record

ord-631430483e924be19e134610c3030daa

Source dataset

uspto-grants-2006_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07129235B2