反应详情

温度

65 °C

A solution containing 7-(((5-chloro-2-nitrophenyl)amino)methyl)-7-methyl-3-neopentyl-1-oxa-3-azaspiro[4.5]decan-2-one (0.100 g, 0.236 mmol) in MeOH (5 mL) was treated with iron (325 mesh) (0.132 g, 2.36 mmol) followed by formic acid (0.090 mL, 2.359 mmol) and trimethyl orthoformate (0.261 mL, 2.359 mmol). The resulting mixture was heated at 65° C. for 18 h. LCMS indicated partial conversion to desired product. Additional iron (0.100 g, 1.79 mmol), formic acid (0.200 mL, 5.22 mmol), and trimethyl orthoformate (0.500 mL, 4.53 mmol) were added, and the reaction was stirred at 80° C. for 3 h. The reaction was cooled to rt and filtered through filter paper. The collected solids were washed with MeOH, and the combined MeOH washings and filtrate were concentrated. The crude product was purified by reverse-phase HPLC (Sunfire Prep C18 column (30×150 mm); 14 minute run; 40 mL/min flow rate with at-column dilution; Solvent A: MeCN/0.1% TFA, Solvent B: water/0.1 TFA, gradient: 10-90% solvent A) to afford the title compound (0.071 g, 52% yield) as the TFA salt. 1H NMR (400 MHz, CDCl3) δ 8.88 (br. s., 1H), 7.89 (d, J=8.78 Hz, 1H), 7.56 (d, J=1.51 Hz, 1H), 7.49 (dd, J=1.63, 8.66 Hz, 1H), 7.27 (s, 1H), 4.08 (s, 2H), 3.26-3.40 (m, 1H), 3.06 (d, J=14.05 Hz, 1H), 2.92 (d, J=14.05 Hz, 1H), 2.05 (br. s., 1H), 1.79-1.99 (m, 2H), 1.69 (d, J=14.05 Hz, 1H), 1.58 (br. s., 1H), 1.42 (d, J=13.80 Hz, 1H), 1.28-1.37 (m, 2H), 1.27 (s, 3H), 0.95 (s, 9H). MS (m/z) 404.2 (M+H+).