Methyl iodide → HCID 58365057, compound

Temperature

-78 °C

To a solution of N,N-diisopropylamine (3.1 mL, 22 mmol) in tetrahydrofuran (60 mL) cooled at −78° C. was added n-butyllithium (2.5N solution in hexanes, 8.9 mL, 22 mmol) dropwise over 5 minutes and the mixture was stirred for 30 minutes at −78° C. A solution of tert-butyl 1-benzylpiperidine-4-carboxylate (5.0 g, 20 mmol) in tetrahydrofuran (40 mL) was then added to the reaction mixture dropwise over 10 min and the temperature was maintained at −78° C. for 30 minutes before methyl iodide (1.3 mL, 21 mmol) was added in one portion. The reaction mixture was warmed to ambient temperature and stirred for 1 hour. The reaction was quenched with water (100 mL) and diluted with ethyl acetate (50 mL). The organic layer was separated and the aqueous layer was extracted with ethyl acetate (3×50 mL). The combined organic portions were dried over sodium sulfate, filtered, concentrated in vacuo, and purified flash chromatography (silica, 40 g, ISCO, 0-100% ethyl acetate in heptanes) to afford the title compound as a colorless oil, which was used in the next step without any further purification (5.3 g, 90%).

1. additionwas added in one portion
2. temperatureThe reaction mixture was warmed to ambient temperature
3. stirringstirred for 1 hour
4. customThe reaction was quenched with water (100 mL)
5. additiondiluted with ethyl acetate (50 mL)
6. customThe organic layer was separated
7. extractionthe aqueous layer was extracted with ethyl acetate (3×50 mL)
8. dry with materialThe combined organic portions were dried over sodium sulfate
9. filtrationfiltered
10. concentrationconcentrated in vacuo
11. custompurified flash chromatography (silica, 40 g, ISCO, 0-100% ethyl acetate in heptanes)

ORD record

ord-e3f19caf5c7244f69f8175fb3b28a8fa

Source dataset

uspto-grants-2016_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09440976B2