p-Toluenesulfonic acid → 5-(Pyridin-2-ylamino)pentanenitrile

Temperature

40 °C

4-(1,3-Dioxolan-2-yl)butanenitrile (6.26 g; 0.0443 moles) was dissolved in a mixture of acetone (50 mL) and water (50 mL) under nitrogen. p-Toluene-sulfonic acid (843 mg; 0.00443 moles) was added followed by sodium periodate (9.67 g; 0.0452 moles) and the mixture was heated at 40° C. for 32 hours with magnetic stirring. The mixture was filtered, washing the filter cake with ethyl acetate (100 mL). The filtrate was mixed with aqueous sodium bicarbonate solution (50 mL) and the phases were separated. The aqueous phase was extracted with ethyl acetate (3×100 mL). The combined organic phases were dried over sodium sulfate and filtered. Removal of solvent under vacuum gave the crude product (5-oxopentanenitrile). This material was dissolved in methylene chloride (150 mL). 2-Aminopyridine (4.17 g; 0.0443 moles) was added and the reaction mixture was magnetically stirred under nitrogen for 30 minutes. Sodium triacetoxyborohydride (14.1 g; 0.0665 moles) was added and the reaction mixture was stirred for 4 hours. The reaction mixture was added to aqueous sodium bicarbonate solution (50 mL) and the phases were separated. The aqueous phase was extracted with ethyl acetate (4×50 mL). The combined organic phases were dried over sodium sulfate and filtered. Removal of solvent under vacuum gave crude product which was purified by chromatography on silica gel, eluting with methylene chloride followed by methylene chloride/acetone (10:1). Removal of solvent under vacuum gave the product, 5-(pyridin-2-ylamino)pentane-nitrile, as an off white solid (4.30 g; 55%). 1H NMR (CDCl3) δ 8.05-8.10 (1H, m), 7.38-7.43 (1H, m), 6.55-6.60 (1H, m), 6.38 (1H, d, J=8.5 Hz), 4.38-4.58 (1H, br), 3.30-3.40 (2H, m), 2.35-2.45 (2H, m), 1.70-1.85 (4H, m).

1. filtrationThe mixture was filtered
2. washwashing the filter cake with ethyl acetate (100 mL)
3. additionThe filtrate was mixed with aqueous sodium bicarbonate solution (50 mL)
4. customthe phases were separated
5. extractionThe aqueous phase was extracted with ethyl acetate (3×100 mL)
6. dry with materialThe combined organic phases were dried over sodium sulfate
7. filtrationfiltered
8. customRemoval of solvent under vacuum
9. customgave the crude product (5-oxopentanenitrile)
10. stirringthe reaction mixture was stirred for 4 hours
11. customthe phases were separated
12. extractionThe aqueous phase was extracted with ethyl acetate (4×50 mL)
13. dry with materialThe combined organic phases were dried over sodium sulfate
14. filtrationfiltered
15. customRemoval of solvent under vacuum
16. customgave crude product which
17. customwas purified by chromatography on silica gel
18. washeluting with methylene chloride
19. customRemoval of solvent under vacuum

ORD record

ord-4865eef5711b41e49ac40ff86075e58e

Source dataset

uspto-grants-2005_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06933304B2