Synthesis
To a solution of tert-butyl (R)-4-methyl-2-benzyl succinate (308 mg, 1.11 mmol) in tetrahydrofuran (THF, 3 mL) was added an aqueous solution (3 mL) of lithium hydroxide (107 mg, 4.44 mmol). The reaction mixture was stirred at room temperature overnight. Completion of the reaction was confirmed by monitoring the progress of the reaction by thin layer chromatography (TLC, unfolding agent: cyclohexane/ethyl acetate = 7/3). The reaction mixture was acidified to pH = 1 with 2 M hydrochloric acid (HCl) and then extracted with dichloromethane (DCM, 2 x 20 mL). The organic layers were combined and the solvent was evaporated after separation by a phase separator. The crude product was purified by fast column chromatography (eluent: cyclohexane/ethyl acetate = 9/1 → 7/3), using the starting eluent as solution loading, to afford (R)-2-benzyl-4-(tert-butoxy)-4-oxobutanoic acid as a colorless oil. Yield: 274 mg (94%), purity > 95%, retention time (rt) = 4.17 min (gradient A), mass spectrum (M + H)+ = 209 (loss of tert-butyl).
