General procedure for the synthesis of methyl 1-tert-butoxycarbonyl-4-piperidinecarboxylate from methanol and 1-Boc-4-piperidinecarboxylic acid: a hexane solution of trimethylmethylsilyl diazomethane (2.00 M, 52.9 mL, 106 mmol) was added slowly and dropwise at 0 °C to a 1-tert-butoxycarbonyl-piperidine-4-carboxylic acid (12.14 g, 52.95 mmol) acetonitrile ( 100 mL) suspension. Methanol (10 mL) was then added. The reaction mixture was allowed to stand at 0 °C for 30 min and then stirred at room temperature for 3 h. The reaction was carried out under reduced pressure. Upon completion of the reaction, the solvent was removed by distillation under reduced pressure. The residue was purified by column chromatography [hexane/ethyl acetate (4.5:1, v/v)] to afford 1-tert-butyl 4-methylpiperidine-1,4-dicarboxylate as a colorless oil (11.5 g, 90% yield). The structure of the product was confirmed by 1H NMR (400 MHz, d6-DMSO): δ 4.02 (dt, 2H, J = 3.5, 13.7 Hz), 3.69 (s, 3H), 2.82 (ddd, 2H, J = 3, 11.5, 14.5 Hz), 2.45 (tt, 1H, J = 3.9, 11.5 Hz), 1.90-1.84 ( m, 2H), 1.67-1.57 (m, 2H), 1.45 (s, 9H). Mass spectral analysis (ES) showed m/z 265.8 (MNa+); calculated value: 243.1 (M).
