Water → HCID 66777957, compound

A solution of 2′,5′-dihydroxyacetophenone (25.0 g), bromomethylcyclopropane (24.43 g), potassium carbonate (27.2 g) in acetonitrile (400 mL) was stirred with heating under reflux for 2.5 hr. Bromomethylcyclopropane (4.4 g) was added to the mixture, and the mixture was further stirred with heating under reflux for 14 hr. The reaction mixture was cooled to room temperature, the insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane-ethyl acetate 100:0-10:90, v/v) to give 1-[5-(cyclopropylmethoxy)-2-hydroxyphenyl]ethanone (35.5 g) as a yellow oil at purity 70%. A solution of the obtained 1-[5-(cyclopropylmethoxy)-2-hydroxyphenyl]ethanone (35.5 g), 1-bromo-3-methylbutan-2-one (35.5 g) synthesized above and potassium carbonate (66.3 g) in N,N-dimethylformamide (350 mL) was stirred at room temperature for 1 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. 1,8-Diazabicyclo[5.4.0]undec-7-ene (22.5 mL) and N,N-dimethylformamide (300 mL) were added to the obtained residue, and the mixture was stirred at 100° C. for 30 min. The reaction mixture was cooled to room temperature, 1N hydrochloric acid (300 mL) was added, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane-ethyl acetate 100:0-90:10, v/v) to give the title compound (19.91 g, 45%) as a colorless solid.

1. extractionthe mixture was extracted with ethyl acetate
2. washThe extract was washed with saturated brine
3. dry with materialdried over magnesium sulfate
4. concentrationconcentrated under reduced pressure
5. addition1,8-Diazabicyclo[5.4.0]undec-7-ene (22.5 mL) and N,N-dimethylformamide (300 mL) were added to the obtained residue
6. stirringthe mixture was stirred at 100° C. for 30 min
7. temperatureThe reaction mixture was cooled to room temperature
8. addition1N hydrochloric acid (300 mL) was added
9. extractionthe mixture was extracted with ethyl acetate
10. washThe extract was washed with saturated brine
11. dry with materialdried over magnesium sulfate
12. concentrationconcentrated under reduced pressure
13. customThe residue was purified by silica gel column chromatography (hexane-ethyl acetate 100:0-90:10

ORD record

ord-fc17e96683134e8ebea14354d0a4fc55

Source dataset

uspto-grants-2013_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08436043B2