(2R,4S)-4-hydroxypyrrolidine-2-carboxylic acid (1; 10 g, 76.3 mmol) was used as raw material and dissolved in 200 mL of methanol. Under stirring conditions, acetyl chloride (7.6 mL, 106.8 mmol) was slowly added, followed by heating the reaction mixture to reflux overnight. Upon completion of the reaction, the mixture was cooled to room temperature and 500 mL of ether was added to induce crystallization. The white crystals formed were collected by filtration and dried under vacuum to ultimately afford methyl (2R,4S)-4-hydroxypyrrolidine-2-carboxylate hydrochloride (Compound 2; 12.7 g, 87.6% yield).
