2,5-Diazabicyclo[2.2.2]octane synthesis

Yield:-

Reaction Conditions:

Stage #1:2,5-diazabicyclo<2.2.2>octane-3,6-dione with lithium aluminium tetrahydride in tetrahydrofuran for 16 h;Heating / reflux;
Stage #2: with sodium hydroxide;water in tetrahydrofuran at 20; for 1 h;

Steps:

129
Example 129. 2,5-Diazabicyclo [2.2.2] octane (129); [0515] A soxhlet extractor thimble was charged with diketopiperazine 128 (100 mg,0.71 mmol), then placed inside a soxhlet suspended above a flask containing a solution of LAH (4.3 mL, 4.30 mmol, 1.0 M in THF) in THF (100 mL). The system was then heated at reflux for 16 h. Once cooled to 0 ⁰C, the reaction mixture was quenched via the addition of water (200 μL), 4 M NaOH (200 μL) then more water (600 μL). On stirring the resultant suspension at rt for 1 h, the mixture was dried (Na₂SO₄), filtered, and the filter cake washed with THF (100 mL). The combined filtrates were evaporated to afford the title product as a pale yellow oil: ¹H NMR δ_H (250 MHz, CDCl₃) 4.95 (2H, br s), 3.20 (2H, dt), 3.02 (2H, dd), 2.79 (2H, m), 1.71-1.83 (4H, m).

References:

PANACOS PHARMACEUTICALS, INC.;NITZ, Theodore, J.;SALZWEDEL, Karl;FINNEGAN, Catherine;WILD, Carl;BRUNTON, Shirley;FLANAGAN, Stuart;MONTALBETTI, Christian;COULTER, Thomas, Stephen;KIMBER, Marc;MAGARACI, Filippo;JOHNSTON, David WO2008/134035, 2008, A1 Location in patent:Page/Page column 195-196

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