Imidazole → Benzyl 4-iodopiperidine-1-carboxylate

Iodine (17.6 g, 69.2 mmol) was added dropwise as a solution in THF (40 mL) over 1 hour to an ice cold solution of benzyl 4-hydroxypiperidine-1-carboxylate (15.5 g, 65.9 mmol), imidazole (4.71 g, 69.2 mmol), and triphenylphosphine (18.2 g, 69.2 mmol) in THF (40 mL). This resulting red solution was stirred overnight with warming to room temperature, then cooled back to 0° C. before being quenched with 10% aqueous sodium sulfite. The resulting biphasic mixture was separated and the aqueous layer was extracted with ethyl acetate (1×). The combined extracts were dried over magnesium sulfate (MgSO4), filtered, and concentrated in vacuo to give an oil that was purified by silica gel chromatography (10% EtOAc/hexane) to give benzyl 4-iodopiperidine-1-carboxylate as a coloreless oil (9.50 g, 42% yield).

1. temperaturecooled back to 0° C.
2. custombefore being quenched with 10% aqueous sodium sulfite
3. customThe resulting biphasic mixture was separated
4. extractionthe aqueous layer was extracted with ethyl acetate (1×)
5. dry with materialThe combined extracts were dried over magnesium sulfate (MgSO4)
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customto give an oil that
9. customwas purified by silica gel chromatography (10% EtOAc/hexane)

ORD record

ord-63edbce632404acca316989b42a506e9

Source dataset

uspto-grants-2016_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09376450B2