GENERAL STEPS: 37% formaldehyde aqueous solution (1.26 mL, 16.9 mmol) was slowly added to a suspension of (2R)-piperidine-2-carboxylic acid (2.00 g, 15.5 mmol) with 5% Pd/C (500 mg) in methanol (20 mL). The reaction system was replaced by hydrogen, supplemented with formaldehyde (0.60 mL, 8.06 mmol), and stirred at room temperature for 20 h under hydrogen atmosphere. After completion of the reaction, the mixture was filtered by diatomaceous earth pad extraction and the filter cake was washed by methanol (200 mL). The combined filtrates were concentrated under reduced pressure to give the title compound (R)-1-methyl-2-piperidinecarboxylic acid (2.23 g, quantitative yield) as a white solid, which was used directly in the subsequent reaction. detection by TLC: Rf = 0.25 (unfolding agent V(CH2Cl2)/V(MeOH) = 1:1). Melting point: 208-210°C. Specific optical rotation: [α]D27.1 = +67.6 (c 1.27, methanol). IR spectrum (KBr pressed): 3407, 2950, 1615, 1399 cm-1. 1H NMR (400 MHz, CDCl3): δ 8.22 (broad peak, 1H), 3.64 (d, 1H, J = 12.0 Hz), 3.28 (multiple peaks, 1H), 2.86 (s, 3H), 2.70 (multiple peaks, 1H), 2.34 (d, 1H, J = 14.4 Hz), 2.00-1.74 (multiple peaks, 4H), 1.46 (multiple peaks, 1H).13C NMR (100 MHz, DMSO-d6): δ 170.4, 68.3, 53.3, 42.3, 28.0, 23.1, 21.8.High-resolution mass spectrometry (ESI): m/z calculated value C7H13NO2 [M]+ 143.0946, measured value 143.0947.
