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

4-Hydroxypiperidine (50 g) was added portionwise to a stirred suspension of potassium tert-butoxide (110.9 g) in THF (900 mL) at room temperature and under nitrogen. The mixture was heated at reflux and 1,2-dichloro-4-fluorobenzene (98 g) added dropwise over 30 min. The mixture was stirred at reflux for another 1 h 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 over 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 h
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 over 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-742f8aa8377949b683075e327afaab7d

Source dataset

uspto-grants-2011_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07956070B2