Toluene → 4-(5-Cyclopropyl-3-methylpyridin-2-yl)piperazine-1-carboxylic acid tert-butyl ester

To a mixture of 4-(5-bromo-3-methylpyridin-2-yl)piperazine-1-carboxylic acid tert-butyl ester (3.6 g), bis(tricyclohexylphosphine)palladium(II)dichloride (396 mg), tripotassium phosphate (12 g) and cyclopropylboronic acid (2.1 g) were added toluene (30 mL) and water (1.5 mL), and the mixture was stirred with heating under reflux for 8 hr. The reaction mixture was cooled, water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and the solvent was evaporated. The obtained residue was purified by column chromatography (chloroform) to give 4-(5-cyclopropyl-3-methylpyridin-2-yl)piperazine-1-carboxylic acid tert-butyl ester (2.2 g). The obtained 4-(5-cyclopropyl-3-methylpyridin-2-yl)piperazine-1-carboxylic acid tert-butyl ester (2.2 g) was dissolved in chloroform (5 mL), 4N hydrogen chloride/ethyl acetate (5 mL) was added, and the mixture was stirred at room temperature overnight. To the reaction mixture was added ethyl acetate (20 mL), and the precipitate was collected by filtration to give the title compound (1.3 g).

1. temperaturewith heating
2. temperatureunder reflux for 8 hr
3. temperatureThe reaction mixture was cooled
4. extractionthe mixture was extracted with ethyl acetate
5. washThe organic layer was washed with saturated brine
6. customthe solvent was evaporated
7. customThe obtained residue was purified by column chromatography (chloroform)

ORD record

ord-8027c34761884ff582fc70cc8ec71727

Source dataset

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08816079B2