General procedure for the synthesis of 4-methyl 2,2-dimethylbutanedioate from methanol and 2,2-dimethylsuccinic acid:
Step 1. Preparation of 4-methoxy-2,2-dimethyl-4-oxobutanoic acid
To a stirred solution of 2,2-dimethylsuccinic acid (4.5 g, 31 mmol) in methanol (45 mL) was added 98% H2SO4 (0.45 mL) dropwise at 0°C. The reaction mixture was then stirred at room temperature for 16 hours. Upon completion of the reaction, the solution was concentrated. To the residue was added saturated aqueous NaHCO3 solution (20 mL) and washed with hexane (50 mL x 3). The aqueous phase was then adjusted to pH=2 with 6N HCl, extracted with ethyl acetate (200 mL x 4), and the organic phase was dried with Na2SO4 and concentrated. 2,2-Dimethylbutanedioic acid 4-methyl ester (2.5 g, 51% yield) was obtained as a colorless oil without further purification.
1H NMR (500 MHz, CDCl3): δ 3.65 (s, 3H), 2.61 (s, 2H), 1.27 (s, 6H) ppm.
