Methyl iodide → 1-tert-Butyl 4-ethyl 4-methylpiperidine-1,4-dicarboxylate

Temperature

-78 °C

A solution of O1-tert-butyl O4-ethyl piperidine-1,4-dicarboxylate (1.5 g, 5.84 mmol) in THF (25 mL) was cooled to −78° C. followed by dropwise addition of LDA (1.80 M in THF, 6.5 mL, 11.68 mmol) at −78° C. The resulting mixture was stirred at −78° C. for 45 min followed by addition of methyl iodide (1.2 mL, 17.52 mmol). The temperature was slowly raised up to RT and left at RT for 6 h. The reaction was cooled to 0° C. and quenched by the dropwise addition of saturated NH4Cl solution (50 mL). The reaction was extracted with EtOAc (3×100 mL). The combined organics were washed with brine, dried (Na2SO4), filtered and concentrated in vacuo. Purification by chromatography on silica eluting with 2% EtOAc in hexane gave i (1.0 g, 65%).

1. temperatureThe temperature was slowly raised up to RT
2. waitleft at RT for 6 h
3. temperatureThe reaction was cooled to 0° C.
4. customquenched by the dropwise addition of saturated NH4Cl solution (50 mL)
5. extractionThe reaction was extracted with EtOAc (3×100 mL)
6. washThe combined organics were washed with brine
7. dry with materialdried (Na2SO4)
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. customPurification by chromatography on silica eluting with 2% EtOAc in hexane
11. customgave i (1.0 g, 65%)

ORD record

ord-766fd136f1904c0bb716fed07d5731b4

Source dataset

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08906902B2