1-Azabicyclo[2.2.2]octane-4-carboxylic acid ethyl ester

869112-14-1

22766-68-3

General procedure: ethyl 1-(2-chloroethyl)piperidine-4-carboxylate (II) (5.0 g, 22.76 mmol) was dissolved in tetrahydrofuran (THF, 147.0 mL) under nitrogen protection and the solution was cooled to -50 °C. At -50 °C, LDA (2.0 M in heptane/THF/ethylbenzene, 17.0 mL, 34.0 mmol) was added slowly over 25 min. The reaction mixture was gradually warmed to room temperature over 16 hours. Upon completion of the reaction, the reaction was quenched with saturated aqueous K2CO3 solution (122.0 mL) and extracted with ether (3 x 120.0 mL). The organic layers were combined, dried with MgSO4, filtered and concentrated under reduced pressure. The resulting orange liquid was co-evaporated three times with dichloromethane to remove excess ethylbenzene, resulting in an orange oily product (4.15 g, 99.4% yield). The product was ethyl 1-azabicyclo[2.2.2]octane-4-carboxylate (III) with the following 1H-NMR (300 MHz, CDCl3) data: δ4.10 (t, J=5.23 Hz, 2H), 2.90-2.85 (m, 6H), 1.71-1.66 (m, 6H), 1.22 (t, J=4.0 Hz, 3H).