Potassium Carbonate → 4-(4-Chlorophenyl)-1-(3,3-diphenyl-propyl)-4-fluoropiperidine

Temperature

80 °C

A solution of 4-(4-chlorophenyl)-4-fluoropiperidine hydrochloride (100 mg, 0.40 mmol) and 3,3-diphenyl-1-iodopropane (145 mg, 0.45 mmol) in DMF (2.5 mL) was treated with potassium carbonate (560 mg, 4.05 mmol) and the resulting suspension heated at 80° C. for 14 hours. After this time the reaction was cooled to room temperature and quenched by pouring into 25% aqueous ammonium chloride solution (20 mL). The resulting suspension was then extracted with ethyl acetate (2×10 mL) and the combined extracts washed with water (10 mL) and brine (10 mL) then dried over magnesium sulfate. Subsequent filtration and concentration under reduced pressure afforded crude 4-(4-chlorophenyl)-1-(3,3-diphenyl-propyl)-4-fluoropiperidine as a yellow oil. This material was treated with 10% methanolic hydrogen chloride (10 mL) and the solution concentrated under reduced pressure. Trituration of the resulting oil with 1:1 ethyl acetate/2-butanone (10 mL) afforded a solid which was isolated by filtration and vacuum dried. This afforded a 41% yield of 4-(4-chlorophenyl)-1-(3,3-diphenylpropyl)-4-fluoropiperidine hydrochloride as an off-white solid.

1. temperatureAfter this time the reaction was cooled to room temperature
2. customquenched
3. additionby pouring into 25% aqueous ammonium chloride solution (20 mL)
4. extractionThe resulting suspension was then extracted with ethyl acetate (2×10 mL)
5. washthe combined extracts washed with water (10 mL) and brine (10 mL)
6. dry with materialthen dried over magnesium sulfate
7. filtrationSubsequent filtration and concentration under reduced pressure

ORD record

ord-dc7a507a742d4592a8486e6fa6270869

Source dataset

uspto-grants-2014_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08859777B2