The general procedure for the synthesis of (2S,5S)-5-hydroxypiperidine-2-carboxylic acid hydrochloride from the compound (CAS:1383814-52-5) is as follows:
Step 1: Preparation of (2S,5S)-5-hydroxypiperidine-2-carboxylic acid hydrochloride
(2S,5S)-5-hydroxypiperidine-2-carboxylic acid tert-butyl ester (126.22 g, 0.63 mol) was gradually added to 5 M hydrochloric acid (630 mL) at room temperature, followed by heating to 65 °C and stirring for 2 hours. Upon completion of the reaction, the reaction solution was cooled to room temperature and the solvent was removed by concentration under reduced pressure. The residue was dissolved in water (500 mL), activated carbon (6.5 g) was added and stirred at room temperature for 30 minutes. The activated carbon was removed by diatomaceous earth filtration and the diatomaceous earth was washed twice with (100 mL) water, the filtrates were combined and concentrated under reduced pressure. The resulting residue (150 g) was cooled in an ice bath, inoculated and stirred. Acetone (650 mL) was added slowly and dropwise over 30 minutes and stirring was continued for 30 minutes. The precipitated crystals were filtered under argon protection and washed with acetone. The crystals were dried under vacuum overnight to give 108.79 g of (2S,5S)-5-hydroxypiperidine-2-carboxylic acid hydrochloride as colorless powdery crystals (96% yield).
1H NMR (400 MHz, D2O) δ 1.66-2.23 (m, 4H), 3.25 (d, J = 3.4 Hz, 1H), 3.38 (d, J = 3.4 Hz, 1H), 4.00 (dd, J = 11.7, 3.7 Hz, 1H), 4.22 (brs, 1H); MS m/z: 146 (M-HCl + H)+.
