Step 2. Hydrolysis reaction: To a mixed solution of methyl 1-Boc-3-methylpiperidine-3-carboxylate (15.86 g, 0.062 mol) in THF (100 ml) and water (10 ml), lithium hydroxide monohydrate (LiOH-H2O, 7.76 g, 0.186 mol) was added at room temperature. The reaction mixture was heated to 70 °C and refluxed for 6 hours. The progress of the reaction was monitored by TLC (unfolding agent: petroleum ether/ethyl acetate, 4:1, iodine color development), and after confirming that the raw material was completely consumed, the mixture was concentrated to dryness. The residue was diluted with deionized water (300 mL) and subsequently extracted with methyl tert-butyl ether (MTBE, 100 mL x 2) and the organic layer was discarded. The aqueous layer was acidified to pH 1 with 1 M aqueous hydrochloric acid and extracted with MTBE (100 mL × 2). The organic layers were combined, washed with saturated brine, dried over anhydrous sodium sulfate and concentrated to dryness to give 1-Boc-3-methylpiperidine-3-carboxylic acid (13.97 g, 93% yield) as a white solid.
