Water → HCID 57486371, compound

Temperature

50 °C

To a solution of 4-chloro-3-trifluoromethylpyridine hydrochloride salt (2.0 g) in tetrahydrofuran (5 mL) were added sodium hydride (60%, 2.8 g) and propan-2-ol (2.8 g), and the mixture was stirred at 50° C. for 2 hours. After cooling to room temperature, to the reaction mixture was added water, and the resulting mixture was extracted with diethyl ether. The organic layer was dried over magnesium sulfate, and concentrated. The residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate) to give 4-isopropoxy-3-trifluoromethylpyridine (1.5 g). To a solution of the obtained compound (1.5 g) in ethyl acetate (20 mL) was added 4-bromomethylbenzoic acid methyl ester (2.0 g) at room temperature, and the mixture was heated under reflux overnight. After cooling to room temperature, the solvent was removed to give 4-isopropoxy-1-(4-methoxycarbonylbenzyl)-3-trifluoromethyl-pyridinium bromide (2.1 g). To a solution of the obtained compound (2.1 g) in dimethoxyethane (10 mL) were added acrylonitrile (1.3 g), manganese dioxide (2.1 g) and triethylamine (1.5 g), and the mixture was stirred at 80° C. for 6 hours. The reaction mixture was filtered through a Celite pad, and filtrate was concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate) to give the title compound (0.04 g).

1. temperatureAfter cooling to room temperature, to the reaction mixture
2. extractionthe resulting mixture was extracted with diethyl ether
3. dry with materialThe organic layer was dried over magnesium sulfate
4. concentrationconcentrated
5. customThe residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate)

ORD record

ord-0fba5e6970664beba53b6b1499d31957

Source dataset

uspto-grants-2014_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08748452B2