General procedure: 500 mg of hydroxyphthalimide (Aldrich) was dissolved in 5 mL of dimethylformamide (DMF) under argon protection, followed by the addition of 0.2 mL of methylene iodide (Aldrich) and 0.5 mL of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU, Aldrich) sequentially, slowly dropwise. The reaction mixture was stirred at 60 °C for 2 h and then cooled to room temperature and the reaction was quenched by addition of 2 N hydrochloric acid solution. The reaction solution was diluted with 20 mL of ethyl acetate, dried over magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure and the residue was purified by silica gel column chromatography using ethyl acetate/hexane (1:5, v/v) as eluent and dried to give 407 mg of the target compound (yield: 75%). The compound was dissolved in 5 mL of dichloromethane and 0.11 mL of methylhydrazine (TCI) was slowly added at 0 °C. The reaction solution was stirred at room temperature for 2 hours and then cooled to 0°C again. The resulting solid was collected by filtration and 1 mL of 4 M dioxane hydrochloride solution (Aldrich) was added to the filtrate, filtered and dried to give 173 mg of solid product (yield: 90%). Under argon protection, 10 mg of the above solid was dissolved with 54 mg of SAC-0906 in 1 mL of pyridine (Aldrich) and stirred at 80 °C for 4 hours. After the reaction solution was cooled to room temperature, it was acidified by adding 2 N hydrochloric acid solution, extracted with 20 mL of ether, dried over magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure and the residue was purified by silica gel column chromatography using ethyl acetate/hexane (1:5, v/v) as eluent to give the final methoxyamine hydrochloride SAC-1012 (48 mg, yield: 85%).1H-NMR (300 MHz, CDCl3) δ 5.91-5.76 (m, 2H), 5.34-5.32 (m, 1H) , 5.28-5.24 (m, 1H), 5.15 (m, 1H), 4.24-4.07 (m, 3H), 3.80 (s, 3H), 3.58-3.48 (m, 1H), 2.42-0.60 (m, 35H).
