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

Boiling point:

233.4±40.0 °C(Predicted)

Density 

1.09±0.1 g/cm3(Predicted)

storage temp. 

Sealed in dry,Room Temperature

pka

9.44±0.12(Predicted)

Appearance

Colorless to light yellow Liquid

InChI

InChI=1S/C10H17NO2/c1-2-13-9(12)10-3-6-11(7-4-10)8-5-10/h2-8H2,1H3

InChIKey

MMXIVBVOFFBDEB-UHFFFAOYSA-N

SMILES

N12CCC(C(OCC)=O)(CC1)CC2

Safety Information

HS Code 

2933998090

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

Uses

Ethyl 4-Quinuclidinecarboxylate is a reactant used in the synthesis of azoniabicyclooctanes as muscarinic acetylcholine receptor antagonists.

Synthesis

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).

References

[1] Patent: WO2018/87561, 2018, A1. Location in patent: Page/Page column 13
[2] Patent: US2007/185155, 2007, A1. Location in patent: Page/Page column 9
[3] Journal of Medicinal Chemistry, 2009, vol. 52, # 8, p. 2493 - 2505
[4] Patent: WO2005/112644, 2005, A2. Location in patent: Page/Page column 13
[5] Angewandte Chemie - International Edition, 2017, vol. 56, # 4, p. 1152 - 1157

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