Water → 4-(3,4-Dichlorophenoxy)piperidine

A thin slurry of 4-hydroxypiperidine (50 g, 494 mmol) in THF (200 ml) was added to a stirred suspension of potassium tert-butoxide (110.9 g, 990 mmol) in THF (650 ml) at room temperature and washed in with THF (50 ml). The resultant mixture was stirred under nitrogen for 20 minutes. 1,2-Dichloro-4-fluorobenzene (98 g, 594 mmol) was added and the resultant mixture heated at reflux for 90 minutes. The reaction mixture was cooled to room temperature and water (500 ml) added. The layers were separated and the solvent removed from the organic fraction. The material was then partitioned between MTBE and 10% aqueous citric acid solution. The layers separated and the aqueous layer washed with further MTBE (2×250 ml). The aqueous phase was basified to pH>10 by addition of 10N NaOH solution and the product extracted with iso-propyl acetate (2×30 ml). The organics were washed with brine (300 ml), 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 (109.1 g, 90%).

1. washwashed in with THF (50 ml)
2. temperatureat reflux for 90 minutes
3. customThe layers were separated
4. customthe solvent removed from the organic fraction
5. customThe material was then partitioned between MTBE and 10% aqueous citric acid solution
6. customThe layers separated
7. washthe aqueous layer washed with further MTBE (2×250 ml)
8. additionThe aqueous phase was basified to pH>10 by addition of 10N NaOH solution
9. extractionthe product extracted with iso-propyl acetate (2×30 ml)
10. washThe organics were washed with brine (300 ml)
11. dry with materialdried over magnesium sulfate
12. filtrationfiltered
13. concentrationconcentrated under vacuum

ORD record

ord-11afab28db224ebfb8bd415eef664845

Source dataset

uspto-grants-2010_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07709500B2