Water → 5-[4-[1-(4-Methylphenylsulfonyl)piperidin-4-yl]phenyl]pentanoic acid

Temperature

60 °C

To a suspension of (3-carboxypropyl)triphenyl-phosphonium bromide (16.5 g) in THF (170 ml) was added at room temperature potassium t-butoxide (8.63 g), and the mixture was stirred at 60° C. for 10 minutes and then cooled to room temperature. To the mixture was added a solution of 4-[1-(4-methylphenylsulfonyl)piperidin-4-yl]benzaldehyde (4.40 g) in THF (20 ml), and the mixture was stirred at 60° C. for 1 hour. To the mixture was added water (80 ml) and the mixture was extracted with toluene (80 ml). To the aqueous layer was added 1N hydrochloric acid to make the solution pH 3, and the mixture was extracted with ethyl acetate. The organic layer was washed three times with 2% sodium bicarbonate solution, and then with 1N hydrochloric acid and saturated brine (×3). Under reduced pressure, the mixture was concentrated, and the residue was dissolved in THF (150 ml). To the mixture was added Pd—C (0.5 g), and the mixture was stirred under hydrogen atmosphere for 5 hours. By filtration Pd—C was removed, and the filtrate was concentrated under reduced pressure. The resulting crystals were collected by filtration, which were washed with hexane to give colorless crystals of 5-[4-[1-(4-methylphenylsulfonyl)piperidin-4-yl]phenyl]pentanoic acid (4.63 g).

1. temperaturecooled to room temperature
2. stirringthe mixture was stirred at 60° C. for 1 hour
3. extractionthe mixture was extracted with toluene (80 ml)
4. additionTo the aqueous layer was added 1N hydrochloric acid
5. extractionthe mixture was extracted with ethyl acetate
6. washThe organic layer was washed three times with 2% sodium bicarbonate solution
7. concentrationUnder reduced pressure, the mixture was concentrated
8. dissolutionthe residue was dissolved in THF (150 ml)
9. additionTo the mixture was added Pd—C (0.5 g)
10. stirringthe mixture was stirred under hydrogen atmosphere for 5 hours
11. filtrationBy filtration Pd—C
12. customwas removed
13. concentrationthe filtrate was concentrated under reduced pressure
14. filtrationThe resulting crystals were collected by filtration, which
15. washwere washed with hexane

ORD record

ord-fb37d7f70dd140ae9468111d8587ae94

Source dataset

uspto-grants-2001_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06268354B1