反应详情

温度

-78 °C

A solution of 1-tert-butyl 4-methyl piperidine-1,4-dicarboxylate (3.6 g, 14.9 mmol) in THF (100 mL) was cooled to −78° C. under nitrogen and then charged with neat chloroiodomethane (1.8 mL, 24.7 mmol). A solution of methyllithium (16.5 mL, 1.5 M in Et2O) was added dropwise. The reaction was stirred for 60 min at −78° C. and then quenched with half-saturated NH4Cl. After warming to room temperature, the mixture was extracted twice with EtOAc. The organic phases were combined, washed with brine, dried (Na2SO4), filtered, and concentrated in vacuo to yield impure tert-butyl 4-(2-chloroacetyl)piperidine-1-carboxylate as a dark oil. Key non-solvent resonances in 1H-NMR (400 MHz, d6-DMSO) δ=4.68 (s, 2H), 4.1-3.8 (m, 4H), 2.75 (m, 1H), 1.8 (m, 1H), 1.7-1.5 (m, 2H), 1.4 (s, 9H), 1.4-1.2 (m, 2H).

1. customquenched with half-saturated NH4Cl
2. temperatureAfter warming to room temperature
3. extractionthe mixture was extracted twice with EtOAc
4. washwashed with brine
5. dry with materialdried (Na2SO4)
6. filtrationfiltered
7. concentrationconcentrated in vacuo