Water → 1-[(2-Methoxy-3-pyridyl)methyl]-4-[2-oxo-2-(2-trifluoroacetylaminophenyl)ethyl]piperidine

Temperature

-78 °C

482 mg of 2-bromo-N-(trifluoroacetyl)aniline was dissolved in a mixed solvent of 1.8 ml of tetrahydrofuran and 1.8 ml of diethyl ether, and a 1.14M methyllithium diethyl ether solution was added dropwise thereinto at 0° C. After stirring for 10 minutes, the mixture was slowly charged by a cannular to a solution of 2.4 ml of 1.51 M tert-butyllithium and 4 ml of a diethyl ether solution cooled at −78° C. The mixture was stirred for 1 hour. Then, a mixed solution of 500 mg of N1-methoxy,N1-ethyl-2-[1-(2-methoxy-3-pyridyl)methyl]-4-piperidyl]acetamide obtained in Example 55 and 2 ml of tetrahydrofuran was added dropwise thereinto, and the mixture was further stirred for 20 minutes. Water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, and then dried over anhydrous magnesium sulfate. The solvent was evaporated, and the crude product was purified by silica gel column chromatography (ethyl acetate), to give 150 mg of the above compound as a yellow oil.

1. customat 0° C
2. stirringThe mixture was stirred for 1 hour
3. stirringthe mixture was further stirred for 20 minutes
4. extractionthe mixture was extracted with ethyl acetate
5. washThe organic layer was washed with brine
6. dry with materialdried over anhydrous magnesium sulfate
7. customThe solvent was evaporated
8. customthe crude product was purified by silica gel column chromatography (ethyl acetate)

ORD record

ord-5fe8433145b345158fc9d583bd99c979

Source dataset

uspto-grants-2004_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06784192B2