The general procedure for synthesizing trans-4-hydroxy-L-proline methyl ester hydrochloride from methanol and trans-4-hydroxy-L-proline hydrochloride is as follows:
Example 1: (2S,4R)-4-hydroxy-2-pyrrolidine carboxylic acid hydrochloride (1.0 g, 7.6 mmol) was dissolved in methanol (25 mL) and cooled to 0°C. Thionyl chloride (0.83 mL, 11.4 mmol) was added slowly under stirring. The reaction mixture was gradually warmed to room temperature and subsequently heated to reflux overnight. After completion of the reaction, it was cooled to room temperature and the reaction mixture was concentrated to dryness under reduced pressure to afford trans-4-hydroxy-L-proline methyl ester hydrochloride (1.2 g, 92% yield) in white solid form. The structure of the product was confirmed by 1H NMR (300 MHz, DMSO-d6).
[1] Organic Letters, 2018, vol. 20, # 1, p. 162 - 165
[2] Patent: WO2013/174937, 2013, A1. Location in patent: Page/Page column 74
[3] Patent: US2015/152048, 2015, A1. Location in patent: Paragraph 0447-0448