Hydrochloric Acid → HCID 86760808, compound

Temperature

85 °C

To a dry 2 L three-necked flask under a flow of N2 containing magnesium turnings (13.579 g; 558.69 mmol) in dry THF (165 mL) at reflux (temperature of bath oil of 85° C.), an activating, small amount of 1-bromo-4-[(4-hexylphenyl) ethynyl] benzene (VIIb) (10.400 g; 30.474 mmol) was added in one portion. N2 flow and stirring were stopped. Reaction mixture was heated at reflux for 5 minutes, then several iodine crystals were added keeping vigorous reflux to start the reaction. The reaction mixture went colorless after 5 minutes and reaction mixture turned black-green after an additional minute. A solution of the remaining amount of 1-bromo-4-[(4-hexylphenyl) ethynyl] benzene (VIIb) (162.94 g; 477.42 mmol) in dry THF (360 mL) was added drop wise over 40 minutes into the reaction mixture while keeping gentle reflux. Reflux was maintained for 20 minutes then temperature was allowed to cool to room temperature under stirring for 2 h30. The reaction mixture was cooled to 3° C. and a solution of dry 1-formyl-piperidine (84.60 mL; 761.85 mmol) in dry THF (360 mL) was added drop wise over 1 hour maintaining temperature at 5° C. (maximum temperature: 7.3° C.). The reaction mixture was then allowed to warn to room temperature and it was stirred overnight. The reaction mixture was cooled to 18° C. and 3N HCl (300 mL) was added until the solution was acidic (pH=1). Water was added (500 mL) and extraction was performed with MTBE (500 mL×3). Organic phase was washed successively with water (500 mL×2), saturated solution of NaHCO3 (500 mL×1) and brine (500 mL×1). It was then dried over MgSO4, filtered and concentrated to give an orange solid. It was taken up in Pet ether (400 mL) and left at 4° C. After 16 h the suspension was filtered and washed with Pet ether (2×300 mL) to give after drying under vacuum the first crop m=105.76 g. Filtrate was concentrated and taken up in Pet ether (100 mL). The resulting solid was washed with Pet ether (2×100 mL), and dried to give the second crop m=6.0 g. The title compound was obtained as a white solid (m=111.76 g) in a 76% yield. Melting point: 80° C.

1. customReaction mixture
2. temperaturewas heated
3. temperatureat reflux for 5 minutes
4. temperaturekeeping vigorous reflux
5. customthe reaction
6. customreaction mixture
7. temperatureReflux
8. temperaturewas maintained for 20 minutes
9. temperatureto cool to room temperature
10. temperatureThe reaction mixture was cooled to 3° C.
11. temperaturemaintaining temperature at 5° C. (maximum temperature: 7.3° C.)
12. customto warn to room temperature
13. stirringit was stirred overnight
14. temperatureThe reaction mixture was cooled to 18° C.
15. extraction(500 mL) and extraction
16. washOrganic phase was washed successively with water (500 mL×2), saturated solution of NaHCO3 (500 mL×1) and brine (500 mL×1)
17. dry with materialIt was then dried over MgSO4
18. filtrationfiltered
19. concentrationconcentrated
20. customto give an orange solid
21. waitleft at 4° C
22. filtrationAfter 16 h the suspension was filtered
23. washwashed with Pet ether (2×300 mL)
24. customto give
25. customafter drying under vacuum the first crop m=105.76 g
26. concentrationFiltrate was concentrated
27. washThe resulting solid was washed with Pet ether (2×100 mL)
28. customdried
29. customto give the second crop m=6.0 g

ORD record

ord-1cb998b3ca8e4657b98ad74ff1b79e71

Source dataset

uspto-grants-2009_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07479575B2