Dimethylformamide → 5-Bromo-8-difluoromethoxy-2H-chromen-2-spiro-1'-cyclobutane

Temperature

140 °C

To 48 ml of N,N-dimethylformamide solution containing 10.0 g (27.5 mmol) of 3-bromo-6-difluoromethoxy-2-iodophenol obtained in Reference example 12-(f) were added 0.62 g (2.8 mmol) of palladium acetate, 9.2 g (110 mmol) of sodium hydrogencarbonate and 3.23 g (32.9 mmol) of 1-vinylcyclobutanol (see J. Org. Chem., 1977, 42, 300-305) under argon atmosphere, and the mixture was stirred at 140° C. for 4 hours. After completion of the reaction, water was added to the reaction mixture, and the mixture was extracted with toluene. The organic layer after separation was washed with a saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The obtained residue was applied to silica gel column chromatography (Eluent; hexane:ethyl acetate=9:1 (V/V)), and the fractions containing the desired compound were concentrated under reduced pressure to obtain 0.61 g of the title compound as a pale yellowish oil. (Yield: 70%)

1. additionwas added to the reaction mixture
2. extractionthe mixture was extracted with toluene
3. customThe organic layer after separation
4. washwas washed with a saturated aqueous solution of sodium chloride
5. dry with materialdried over anhydrous sodium sulfate
6. concentrationconcentrated under reduced pressure
7. additionthe fractions containing the desired compound
8. concentrationwere concentrated under reduced pressure

ORD record

ord-5df1695d69c346beae5c9cc2f819831d

Source dataset

uspto-grants-2013_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08450319B2