Ethyl chloroformate → 1-tert-Butyl 4-ethyl 4-cyanopiperidine-1,4-dicarboxylate

Temperatur

-78 °C

A solution of LDA (107 ml, 214.01 mmol) was added to a stirred solution of tert-butyl 4-cyanopiperidine-1-carboxylate (30 g, 143 mmol) in THF (250 ml) at −78° C., under nitrogen. The resulting solution was stirred at −78° C. for 30 minutes. Ethyl chloroformate (16.37 ml, 171.2 mmol) was added. The resulting solution was stirred and allowed to warm to room temperature. The reaction mixture was quenched with saturated NaHCO3 (250 ml), extracted with DCM, and the organic layer was washed with saturated brine (100 ml) then dried over MgSO4, filtered and evaporated to afford the crude material as a orange oil. This material was purified by flash silica chromatography, elution gradient 10% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford 1-tert-butyl 4-ethyl 4-cyanopiperidine-1,4-dicarboxylate (20.8 g, 51.6%) as a yellow oil.

1. stirringThe resulting solution was stirred
2. temperatureto warm to room temperature
3. customThe reaction mixture was quenched with saturated NaHCO3 (250 ml)
4. extractionextracted with DCM
5. washthe organic layer was washed with saturated brine (100 ml)
6. dry with materialthen dried over MgSO4
7. filtrationfiltered
8. customevaporated
9. customto afford the crude material as a orange oil
10. customThis material was purified by flash silica chromatography, elution gradient 10% EtOAc in isohexane
11. customPure fractions were evaporated to dryness

ORD-Eintrag

ord-e521e8be4e0f43de9130e9c71b98b0b5

Quelldatensatz

uspto-grants-2012_01

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08101623B2