Hydrochloric Acid → HCID 12070454, compound

To a suspension of magnesium (0.5 g) in THF (7 ml), a solution of 1-bromo-4-ethoxybenzene (4.0 g) in THF (2.5 ml) was added slowly at room temperature under an argon atmosphere, and the resulting solution was stirred for 1 hour. Subsequently, a solution of trimethoxyborane (2.1 g) in THF (2.5 ml) was added dropwise at −10 to 10° C., and after further addition of THF (7 ml), the reaction mixture was stirred at the same temperature for 1 hour. The reaction mixture was allowed to warm to room temperature and tetrakistriphenylphosphine palladium (115mg), 5-bromo-2-hydroxybenzaldehyde (2.0 g) and an aqueous solution of tripotassium phosphate (11.1 g) in water (15 ml) were added, and the resulting mixture was stirred under reflux for 1 hour. After the mixture was allowed to cool to room temperature, 6N hydrochloric acid (20 ml) was added dropwise, and then toluene(20 ml) was added. After separation, the aqueous phase was further extracted with toluene (30 ml). The organic layers were combined and washed with aqueous 10% sodium chloride solutions (10 ml×3), dried over anhydrous magnesium sulfate and concentrated. The concentrate was purified by silica gel chromatography (n-hexane/ethyl acetate=6/1), and the appropriate eluate was concentrated. Diisopropylether (15 ml) was added to the concentrate and the resulting mixture was heated under reflux, and then allowed to cool to room temperature. n-Hexane (15 ml) was added to the solution, and stirred at room temperature for 1 hour and at 0° C. for 0.5 hour. The precipitated crystal was collected by filtration and washed with diisopropylether/n-hexane (1/1.4 ml) which was previously cooled to 0 to 5° C. Drying under reduced pressure (room temperature, 2 hours) gave yellow crystal of the title compound (1.8 g, yield 73%).

1. stirringthe reaction mixture was stirred at the same temperature for 1 hour
2. stirringthe resulting mixture was stirred
3. temperatureunder reflux for 1 hour
4. temperatureto cool to room temperature
5. customAfter separation
6. extractionthe aqueous phase was further extracted with toluene (30 ml)
7. washwashed with aqueous 10% sodium chloride solutions (10 ml×3)
8. dry with materialdried over anhydrous magnesium sulfate
9. concentrationconcentrated
10. customThe concentrate was purified by silica gel chromatography (n-hexane/ethyl acetate=6/1)
11. concentrationthe appropriate eluate was concentrated
12. additionDiisopropylether (15 ml) was added to the
13. concentrationconcentrate
14. temperaturethe resulting mixture was heated
15. temperatureunder reflux
16. temperatureto cool to room temperature
17. additionn-Hexane (15 ml) was added to the solution
18. stirringstirred at room temperature for 1 hour and at 0° C. for 0.5 hour
19. filtrationThe precipitated crystal was collected by filtration
20. washwashed with diisopropylether/n-hexane (1/1.4 ml) which
21. temperaturewas previously cooled to 0 to 5° C
22. customDrying under reduced pressure (room temperature, 2 hours)

ORD record

ord-4cb8cbd4ed4d4a8dbf1d789db6fe0358

Source dataset

uspto-grants-2006_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07038042B2