Water → 2-Fluoro-5-piperidin-4-ylpyridine

Temperature

-35 °C

A solution of 2-fluoro-5-bromopyridine (7.69 g) in diethyl ether (160 ml) was cooled to −78° C., and into which n-butyl lithium (1,56M-hexane solution, 30 ml) was added dropwise at a temperature not higher than −70° C. After 15 minutes' stirring, tert-butyl 4-oxo-1-piperidinecarboxylate (8.7 g) was added. Temperature of the reaction liquid was raised to −35° C. and water was added, followed by extraction with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. The organic layer was condensed under reduced pressure and isopropyl ether was added to the resulting residue. Whereupon precipitated crystals were recovered by filtration to provide the title compound (4.15 g). The filtrate was purified on column chromatography (hexane/ethyl acetate=3/1-2/1) to provide tert-butyl 4-(6-fluoro-3-pyridinyl)-4-hydroxy-tetrahydro-1(2H)-pyridinecarboxylate (1.25 g).

1. customTemperature of the reaction liquid
2. extractionfollowed by extraction with ethyl acetate
3. washThe organic layer was washed with saturated brine
4. dry with materialdried over anhydrous sodium sulfate
5. customcondensed under reduced pressure and isopropyl ether
6. additionwas added to the resulting residue
7. customWhereupon precipitated crystals
8. filtrationwere recovered by filtration

ORD record

ord-d993797223ee4d3ca68c621030b8b789

Source dataset

uspto-grants-2010_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07727998B2