The general procedure for the synthesis of (R)-4-chloro-3-hydroxybutanoic acid methyl ester from the compound (CAS:114819-45-3) is as follows: to a solution of (R)-3-hydroxybutanoic acid methyl ester (125.1 g, 0.93 mol) in methylene chloride (1.8 L) was added triphenylphosphine (244.5 g, 0.93 mol), and under cooling in an ice-water bath, the N- chlorosuccinimide (124.2 g, 0.93 mol) was added slowly under cooling in an ice water bath. The reaction mixture was stirred at 5 °C for 20 min, followed by continued stirring at room temperature for 18 h. The reaction was carried out at room temperature. Upon completion of the reaction, the solvent was removed by evaporation and the residue was purified by column chromatography (petroleum ether/ethyl acetate, 20:1 to 5:1, gradient elution) to afford the target product (R)-methyl (R)-4-chloro-3-hydroxybutanoate (33 g, three-step overall yield 26%). The product was characterized by 1H NMR (300 MHz, CDCl3): δ 4.18-4.25 (m, 1H), 3.68 (s, 3H), 3.55-3.60 (m, 2H), 3.32-3.33 (d, J = 4.2 Hz, 1H), 2.52-2.68 (m, 2H).
