Dimethylformamide → 1,1-Bis(propan-2-yl) 3,3-dimethoxycyclobutane-1,1-dicarboxylate

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Reaction Conditions

Reaction Steps

Following the procedure of Pigou and Scheisser (J. Org. Chem. 1988, 53, 3841), a 500 mL, 3-neck flask, fitted with a reflux condenser and thermocouple, was charged with NaH (60% in mineral oil, 4 g, 0.210 mol). DMF (100 mL) was added via syringe and the slurry was stirred under N2. Diisopropyl malonate was added at a rate so that the internal temperature did not rise above 70° C. After the H2 evolution had ceased, the flask was briefly opened and 1,3-dibromo-2,2-dimethoxypropane was added. The bath temperature was raised to 145° C. The reaction mixture was maintained at this temperature for 48 h. After this time the dark brown mixture was allowed to cool to rt. Water (50 mL) was added and the solvents were removed in vacuo. The residue was partitioned between ether (200 mL) and sat'd aq NH4Cl (200 mL) and the mixture filtered through a pad of Celite to remove solid impurities. The aqueous layer was extracted with ether (2×100 mL). The combined ether extracts were washed with brine, dried over Na2SO4, filtered and evaporated. Flash chromatography (SiO2, O-25% EtOAc in hexanes) gave semi-pure diisopropyl-3,3-dimethoxycyclobutane-1,1-dicarboxylate (28.5 g), which was used in the next step.

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