1,2-Dichloro-4-fluorobenzene → 4-(3,4-Dichlorophenoxy)piperidine

4-Hydroxypiperidine (50 g, 494 mmol) was added portionwise to a stirred suspension of potassium tert-butoxide (110.9 g, 990 mmol) in THF (900 ml) at room temperature and under nitrogen. The mixture was heated at reflux and 1,2-dichloro-4-fluorobenzene (98 g, 594 mmol) added dropwise over 30 minutes. The mixture was sired at reflux for another 1 hour then cooled down to room temperature, diluted with ethyl acetate (500 ml) and washed with water (500 ml). The organic phase was diluted further with ethyl acetate (500 ml) and extracted with 1M hydrochloric acid (200 ml), The aqueous extract was adjusted to pH>10 by addition of a solution of sodium hydroxide and extracted twice with tert-butylmethyl ether (750 ml). The organic extracts were dried over magnesium sulfate, filtered and concentrated under vacuum to yield the sub-title compound as a dark oil which was used as such in the next step.

1. temperatureThe mixture was heated
2. temperatureat reflux
3. temperatureat reflux for another 1 hour
4. washwashed with water (500 ml)
5. additionThe organic phase was diluted further with ethyl acetate (500 ml)
6. extractionextracted with 1M hydrochloric acid (200 ml)
7. extractionThe aqueous extract
8. additionwas adjusted to pH>10 by addition of a solution of sodium hydroxide
9. extractionextracted twice with tert-butylmethyl ether (750 ml)
10. dry with materialThe organic extracts were dried over magnesium sulfate
11. filtrationfiltered
12. concentrationconcentrated under vacuum

ORD record

ord-9da85e4ef1b543ae9c84d9e686b60415

Source dataset

uspto-grants-2010_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07709500B2