Hydrochloric Acid → 6-(2-Bromo-5-hydroxyphenyl)hex-5-ene-2,4-dione

Temperature

95 °C

Ethyl acetate (3.1 mL), 2,4-pentanedione (4.25 mL, 41.4 mmol) and boron trioxide (2.6 g, 38 mmol) was placed in a 200 mL reaction vessel with a reflux condenser. To the stirring mixture at 85° C. was added dropwise a solution of 2-bromo-5-hydroxybenzaldehyde (1.26 g, 6.27 mmol) and trimethyl orthoformate (0.70 mL, 6.4 mmol) in 6 mL of ethyl acetate. After the reaction mixture was stirred for 30 min at 95° C., n-butylamine (3.1 mL, 31 mmol) was added dropwise with additional stirring for 2 h. The reaction mixture was cooled to 50° C. before addition of 3N HCl (15 mL). After being stirred at 50° C. for 30 min, the mixture was filtered to remove solids. The filtrate was diluted with ethyl acetate, washed with brine twice, and dried over MgSO4. After filtration, the filtrate was concentrated in vacuo, and the residue was purified by silica gel column chromatography (hexane/ethyl acetate=85/15 to 75/25) twice followed by recrystallization (hexane/ethyl acetate) to obtain the title compound as a yellow crystal (0.12 g, 7%).

1. stirringwith additional stirring for 2 h
2. stirringAfter being stirred at 50° C. for 30 min
3. filtrationthe mixture was filtered
4. customto remove solids
5. additionThe filtrate was diluted with ethyl acetate
6. washwashed with brine twice
7. dry with materialdried over MgSO4
8. filtrationAfter filtration
9. concentrationthe filtrate was concentrated in vacuo
10. customthe residue was purified by silica gel column chromatography (hexane/ethyl acetate=85/15 to 75/25)
11. customtwice followed by recrystallization (hexane/ethyl acetate)

ORD record

ord-9966b49ce1b645d585f3ea157b4ff222

Source dataset

uspto-grants-2013_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08552220B2