Potassium Carbonate → HCID 86684921, compound

Temperature

80 °C

4-Bromo-2-methylpyridine (6.0 g, 34.9 mmol) was dissolved in dimethylformamide (60 mL) before potassium acetate (10.0 g, 102 mmol) and 4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi(1,3,2-dioxaborolane) (10 g, 39.4 mmol) were added at room temperature. The solution was degassed and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (400 mg, 547 mol) was added. The brown reaction mixture was stirred for 22 h at 80° C. After cooling to room temperature, 3-(4-bromo-2-trifluoromethyl-phenylsulfanyl)-propionamide (8.0 g, 24.4 mmol), potassium carbonate (8.0 g, 57.9 mmol), dimethylformamide (20 mL), and water (16 mL) were added. The mixture was degassed, stirred for 30 min at room temperature and further [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (400 mg, 547·mol) was added. The resulting brown reaction mixture was stirred for 20 h at 60° C. After cooling to room temperature, it was poured onto water (150 mL) and extracted with ethyl acetate (1×80 mL, 2×40 mL). The combined organic extracts were washed with brine/water (1:1 v/v, mL) and brine (20 mL), methanol (16 mL) was added and the mixture was dried over sodium sulfate. Silica gel (16 g) was added, the slurry was filtered and washed with ethyl acetate/methanol (9:1 v/v, 40 mL). The combined filtrates were concentrated in vacuo. The residue was treated with toluene/n-heptane (1:1 v/v, 24 mL) and the resulting suspension was stirred for 30 min at room temperature. After filtration, the precipitate was washed with toluene/n-heptane (4:1 v/v, 10 mL) and n-heptane (10 mL) and dried in vacuo to afford the title compound as brown crystals (5.7 g, 71%). MS (EI): m/z=341.1 [M+H]+. 1H NMR (d6-DMSO, 400 MHz): δ 2.48 (t, J=7.2 Hz, 2H), 2.54 (s, 3H), 3.32 (t, J=7.2 Hz, 2H), 6.95 (bs, 1H), 7.41 (bs, 1H), 7.58 (dd, J=1.6 Hz, 5.4 Hz, 1H), 7.68 (s, 1H), 7.77 (d, J=9.1 Hz, 1H), 8.02-8.08 (m, 2H), 8.52 (d, J=5.1 Hz, 1H).

1. additionwere added at room temperature
2. customThe solution was degassed
3. temperatureAfter cooling to room temperature
4. customThe mixture was degassed
5. stirringstirred for 30 min at room temperature
6. additionfurther [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (400 mg, 547·mol) was added
7. stirringThe resulting brown reaction mixture was stirred for 20 h at 60° C
8. temperatureAfter cooling to room temperature
9. additionit was poured onto water (150 mL)
10. extractionextracted with ethyl acetate (1×80 mL, 2×40 mL)
11. washThe combined organic extracts were washed with brine/water (1:1 v/v, mL) and brine (20 mL), methanol (16 mL)
12. additionwas added
13. dry with materialthe mixture was dried over sodium sulfate
14. additionSilica gel (16 g) was added
15. filtrationthe slurry was filtered
16. washwashed with ethyl acetate/methanol (9:1 v/v, 40 mL)
17. concentrationThe combined filtrates were concentrated in vacuo
18. additionThe residue was treated with toluene/n-heptane (1:1 v/v, 24 mL)
19. stirringthe resulting suspension was stirred for 30 min at room temperature
20. filtrationAfter filtration
21. washthe precipitate was washed with toluene/n-heptane (4:1 v/v, 10 mL) and n-heptane (10 mL)
22. customdried in vacuo

ORD record

ord-56cb95a71a56409abae3c2b7c81a52b4

Source dataset

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08796471B2