DIETHYL2,5-DIOXOBICYCLO[2.2.2]OCTANE-1,4-DICARBOXYLATE

In the equipment with mechanical stirring, thermometer, dropping a funnel and a condenser tube in a 250 mL four-necked flask, 9.6 g (0.28 mol) of sodium hydride was suspended in 80 mL of ethylene glycol dimethyl ether, 25.6 g (0.1 mol) of diethyl succinylsuccinate was added continuously, 86.8 g (0.46 mol) of 1, 2-dibromoethane was added dropwise at 60 °C, After completion of the drop, the temperature was raised to 90 °C, Continue to stir for 20h to stop the reaction; after the end of the reaction, The dibromide and ethylene glycol dimethyl ether were removed by distillation under reduced pressure, With most of the product of methylene chloride dissolved, the remaining solid with concentrated hydrochloric acid to adjust its PH value is weak acid, Continue to use dichloromethane extraction, desolvation. The crude product was recrystallized from ethanol and the product was 95percent pure and 50percent yield.To a vigorously stirred suspension of NaH (60percent dispersion in mineral oil, 2.54 g, 63.5 mmol) in anhydrous DME (36 mL), t-BuOH (200μL, 2.2 mmol) was added and the mixture was heated to 60 °C under Ar. Diethyl succinate (1) (10 g, 57.4 mmol) was added dropwise over 30 min and the mixture was stirred overnight at 60 °C. The mixture was concentrated under reduced pressure and the resulting pink salt was suspended in distilled dibromoethane (28 mL, 325 mmol). The assembly was transferred to a microwave apparatus and the mixture heated at refluxed temperature by irradiation (80 W) for 12 h under Ar. After cooling, the suspension was filtered and the solid washed with CHCl3 (3 × 10 mL). The filtrate was concentrated under reduced pressure and the residue purified by column chromatography (cyclohexane–EtOAc, 8:2) to afford the title product. Yield: 4.73 g (59percent); white crystals; mp 111 °C. 1H NMR (400 MHz, CDCl3): δ = 1.30 (t, J = 7.2 Hz, 6 H), 2.09–2.15 (m, 2H), 2.46–2.56 (m, 2 H), 2.72 (d, J = 19.4 Hz, 2 H), 3.07 (dd, J = 19.4 Hz, 2.7 Hz, 2 H), 4.26 (q, J = 7.2 Hz, 4 H). 13C NMR (100 MHz, CDCl3): δ = 14.1, 24.5, 41.8, 57.3, 61.8, 168.6 , 203.7.

Molecular Weight:282.29
XLogP3:0.5
Hydrogen Bond Acceptor Count:6
Rotatable Bond Count:6
Exact Mass:282.11033829
Monoisotopic Mass:282.11033829
Topological Polar Surface Area:86.7
Heavy Atom Count:20
Complexity:438
Undefined Atom Stereocenter Count:2
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes