Acetic Acid → (5,6-Dichloro-pyridin-3-yl)-(2,2-dimethoxy-ethyl)-amine

To a Parr bottle was charged Raney Nickel (10.1 g), water (40.0 g), tetrahydrofuran (166.3 g), ethanol (32.0 g) and acetic acid (2.5 g). A solution of 2,3-dichloro-5-nitropyridine (40.0 g) in tetrahydrofuran (40.1 g) was added to the Parr bottle in four portions and the mixture was hydrogenated at 40 psi and 35° C. for about 1 hour after each addition. The reaction mixture was cooled to room temperature, and then glyoxal-1,2-dimethyl acetal (47.2 g of 50 wt % aqueous), tetrahydrofuran (35.6 g) and water (80.4 g) were added and the mixture was hydrogenated at 40 psi and 50° C. for about 12 hours. The reaction was cooled to room temperature and then filtered through a bed of Hy-Flo. The pH of the filtrate was adjusted to 7 with 5% aqueous phosphoric acid, and then the mixture was concentrated. Isopropyl acetate (79 g) was added, this was concentrated, and then more isopropyl acetate (485 g) was added. After warming to 50° C. to dissolve the solids, the solution was washed with 5% aqueous phosphoric acid (3×215 g) and then washed with 20% aqueous sodium chloride solution (231 g). The organic solution was concentrated to about 78 mL and heptane (124 g) was added. After heating to 83° C. to dissolve everything, the solution was slowly cooled to room temperature. More heptane (124 g) was added and then the suspension was cooled to 5° C. After filtering, the wetcake was washed with cold heptane/isopropyl acetate and then dried in the vacuum oven. 1H NMR (400 MHz/CDCl3) δ 7.71 (d, J=2.7 Hz, 1H), 7.01 (d, J=2.7 Hz, 1H), 4.53 (t, J=5.2 Hz, 1H), 4.05 (s, br, 1H), 3.42 (s, 6H), 3.22 (d, J=5.21 Hz, 2H).

1. additionafter each addition
2. waitthe mixture was hydrogenated at 40 psi and 50° C. for about 12 hours
3. temperatureThe reaction was cooled to room temperature
4. filtrationfiltered through a bed of Hy-Flo
5. concentrationthe mixture was concentrated
6. additionIsopropyl acetate (79 g) was added
7. concentrationthis was concentrated
8. additionmore isopropyl acetate (485 g) was added
9. temperatureAfter warming to 50° C.
10. dissolutionto dissolve the solids
11. washthe solution was washed with 5% aqueous phosphoric acid (3×215 g)
12. washwashed with 20% aqueous sodium chloride solution (231 g)
13. concentrationThe organic solution was concentrated to about 78 mL and heptane (124 g)
14. additionwas added
15. temperatureAfter heating to 83° C.
16. dissolutionto dissolve everything
17. temperaturethe solution was slowly cooled to room temperature
18. additionMore heptane (124 g) was added
19. temperaturethe suspension was cooled to 5° C
20. filtrationAfter filtering
21. washthe wetcake was washed with cold heptane/isopropyl acetate
22. customdried in the vacuum oven

ORD record

ord-c675d191661a4eafba0bf6ab57cabcb5

Source dataset

uspto-grants-2009_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07538226B2