Triethylamine → 3-(4-Phenyl-3,6-dihydropyridin-1(2H)-yl)propanoic acid

The 4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (1.5 g, 7.8 mmol) suspended in 16 mL of CH2Cl2. To this suspension was added triethylamine (2.1 mL, 15.3 mmol) followed by methyl 3-bromopropionate (1.0 mL, 9.2 mmol). The reaction was stirred at room temperature for 4 h and at reflux for 2 h. The reaction mixture was washed with water, 1N HCl (2×20 mL), 1N NaOH (2×20 mL) and Brine (1×20 mL). The organic layer was separated, dried over Na2SO4, filtered; and solvent was removed under reduced pressure. To the crude product was added 2N NaOH (15 mL). The mixture was stirred at reflux for 1 h. The reaction mixture was washed with CH2Cl2 (3×20 mL) and neutralized with concentrated HCl. The aqueous solution was concentrated to dryness under reduced pressure, to give a solid residue. Sodium chloride in the residue was removed in the following way (three repeats): dissolving the residue in a minimum amount of water, treating the aqueous solution with acetone, removing the resultant solid material by filtration, and concentrate the filtrate to dryness under reduced pressure. This allowed the isolation of compound Q (159.4 mg).

1. temperatureat reflux for 2 h
2. washThe reaction mixture was washed with water, 1N HCl (2×20 mL), 1N NaOH (2×20 mL) and Brine (1×20 mL)
3. customThe organic layer was separated
4. dry with materialdried over Na2SO4
5. filtrationfiltered
6. customand solvent was removed under reduced pressure
7. additionTo the crude product was added 2N NaOH (15 mL)
8. stirringThe mixture was stirred
9. temperatureat reflux for 1 h
10. washThe reaction mixture was washed with CH2Cl2 (3×20 mL) and neutralized with concentrated HCl
11. concentrationThe aqueous solution was concentrated to dryness under reduced pressure
12. customto give a solid residue
13. customSodium chloride in the residue was removed in the following way (three repeats)
14. dissolutiondissolving the residue in a minimum amount of water
15. additiontreating the aqueous solution with acetone
16. customremoving the resultant solid material
17. filtrationby filtration
18. concentrationconcentrate the filtrate to dryness under reduced pressure

ORD record

ord-7b74e9a64ffa4bd8ad0b8ad77561e551

Source dataset

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08642801B2