Ethanol → Ethyl 2-[2-(3-cyclopropylmethoxy-4-difluoromethoxyphenyl)-2-oxoethyl]-4-(4-methoxybenzyloxy)-3-oxobutyrate

To 460 ml of an ethanol solution containing 13.5 g (50.7 mmol) of ethyl 4-(4-methoxybenzyloxy)-3-oxobutyrate (see WO 2004060890) was added 18.9 ml (50.6 mmol) of 21% sodium ethoxide-ethanol solution under ice-cooling, and the mixture was stirred at room temperature for 1 hour. Then, to the above mixture was added dropwise 300 ml of ethanol solution containing 16.5 g (42.3 mmol) of 2-bromo-1-(3-cyclopropylmethoxy-4-difluoromethoxyphenyl)ethanone obtained in Reference example 45-(a) under ice-cooling, and the mixture was further stirred at 10° C. or lower for 2.5 hours. After completion of the reaction, water was added to the reaction mixture, and the mixture was extracted with chloroform. The organic layer after separation was washed with a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The obtained residue was applied to silica gel column chromatography (Eluent; hexane:ethyl acetate=4:1→7:3 (V/V)), and the fractions containing the desired compound were concentrated under reduced pressure to obtain 14.0 g of the title compound as a pale yellowish oil. (Yield: 63%)

1. temperaturecooling
2. temperaturecooling
3. stirringthe mixture was further stirred at 10° C. or lower for 2.5 hours
4. additionwas added to the reaction mixture
5. extractionthe mixture was extracted with chloroform
6. customThe organic layer after separation
7. washwas washed with a saturated aqueous solution of sodium chloride
8. dry with materialdried over anhydrous magnesium sulfate
9. concentrationconcentrated under reduced pressure
10. additionthe fractions containing the desired compound
11. concentrationwere concentrated under reduced pressure

ORDレコード

ord-4bdbcaef21f741bd948e68e04fe37993

出典データセット

uspto-grants-2013_05

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08450319B2