Step 1 (Synthesis of compound 34-2)
(0217) L-malic acid (80 g, 600 mmol) was dissolved in anhydrous ethanol (500 mL) and thionyl chloride (100 mL, 1.5 mol) was added slowly and dropwise at 0 °C. The reaction mixture was stirred at 0 °C for 20 min, then warmed to room temperature and continued to stir overnight. Upon completion of the reaction, the solvent was removed by concentration under reduced pressure and the residue was extracted with ethyl acetate (1000 mL x 3). The organic phases were combined and washed sequentially with water (500 mL×2) and saturated sodium chloride solution (500 mL×2), and the organic layer was dried with anhydrous sodium sulfate, filtered and concentrated. The crude product was purified by silica gel column chromatography (eluent system: petroleum ether/ethyl acetate = 20:1) to afford diethyl (S)-2-hydroxysuccinate (113 g, 99% yield).
(0218) 1H NMR (400 MHz, CDCl3) δ: 4.47 (q, J = 4.8 Hz, 1H), 4.26 (dq, J = 2.4, 7.2 Hz, 2H), 4.16 (q, J = 7.2 Hz, 2H), 3.28 (d, J = 4.8 Hz, 1H), 2.72-2.89 (m, 2H), 1.20- 1.34 (m, 6H).
