The general procedure for the synthesis of (2S,4S)-N-tert-butoxycarbonyl-4-methylpyrrolidine-2-carboxylic acid from tert-butyl (2S,4S)-2-(hydroxymethyl)-4-methylpyrrolidine-1-carboxylate is as follows: three solutions were prepared prior to oxidation reaction according to the method of Del Valle and Goodman. The first solution was prepared from NaClO2 (1.33 g, 14.7 mmol) dissolved in water (7.4 mL). The second solution was prepared from commercial bleach (436 μL) dissolved in water (7.4 mL). The third solution was prepared by dissolving the feedstock compound (1.60 g, 7.4 mmol) in 100 mL of 3:2 (v/v) acetonitrile/NaH2PO4 buffer (pH 6.6, 0.67 M). The solution containing the feedstock compound was heated to 45°C and TEMPO (193 mg, 0.7 mmol) was added. The two oxidant solutions were added dropwise over a period of 1 h, 618 μL at a time, and the reaction mixture was stirred for 18 h at 40 °C. Upon completion of the reaction, it was cooled to room temperature and the reaction was quenched by dropwise addition of saturated aqueous Na2SO3 solution until the solution became colorless. The acetonitrile was removed by distillation under reduced pressure, and the remaining aqueous solution was alkalized to pH 10 with 1 M NaOH. The alkalized solution was washed with ether (5 x 125 mL) and then acidified to pH 2 with 2 M HCl. The acidified solution was extracted with ether (4 x 200 mL), and the organic layers were combined and dried over anhydrous MgSO4. After concentration under reduced pressure, the target product (1.60 g, 7.0 mmol, 94% yield) was obtained as a white solid.1H NMR (δ): 1.09 (d, J = 6.0 Hz, 3H), 1.44 and 1.50 (s, 9H), 1.58-1.70 and 1.88-2.00 (m, 1H), 2.21-2.31 (m, 1H), 2.31 -2.52 (m, 1H), 2.89-3.04 (m, 1H), 3.67-3.82 (m, 1H), 4.20-4.38 (m, 1H); 13C NMR (δ): 16.9, 17.2, 28.2, 28.3, 32.7, 36.4, 38.8, 53.3, 54.1, 59.4, 59.5, 80.4, 81.6, 159.4 81.6, 159.4, 162.1, 174.9, 179.6; ESI-MS (m/z): [M-H]? Calculated value C11H18NO4, 228.1; measured value: 228.4.
