1-Chloro-4-iodobenzene → tert-Butyl 4-(4-chlorophenyl)-4-hydroxypiperidine-1-carboxylate

Temperature

-78 °C

Into a 1-L 3-necked round-bottom flask, which was purged and maintained with an inert atmosphere of nitrogen, was placed a solution of 1-chloro-4-iodobenzene (10.0 g, 41.9 mmol) in tetrahydrofuran (150 mL). The solution was cooled to −78° C., then n-BuLi (2.4 M) (16.6 mL, 39.8 mmol) was added dropwise and the resulting mixture was stirred for 0.5 h at −78° C. A solution of tert-butyl 4-oxopiperidine-1-carboxylate (7.60 g, 38.1 mmol) in tetrahydrofuran (50 mL) was added dropwise and the resulting mixture was stirred for 1 h at -78° C. The reaction was then warmed to 0° C., and carefully quenched by the slow addition of water (150 mL). The layers were separated and the aqueous phase was extracted with ethyl acetate (150 mL). The combined organic layers were dried (Na2SO4), filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography with ethyl acetate/petroleum ether (1:50 to 1:3) to yield the title compound as a light yellow solid (9.3 g, 78%).

1. customInto a 1-L 3-necked round-bottom flask, which was purged
2. temperaturemaintained with an inert atmosphere of nitrogen
3. stirringthe resulting mixture was stirred for 1 h at -78° C
4. temperatureThe reaction was then warmed to 0° C.
5. customcarefully quenched by the slow addition of water (150 mL)
6. customThe layers were separated
7. extractionthe aqueous phase was extracted with ethyl acetate (150 mL)
8. dry with materialThe combined organic layers were dried (Na2SO4)
9. filtrationfiltered
10. concentrationconcentrated under reduced pressure
11. customThe residue was purified by silica gel column chromatography with ethyl acetate/petroleum ether (1:50 to 1:3)

ORD record

ord-15c6a501ff934b948445a739c782d79d

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09428502B2