1. 500 mg of hydroxyphthalimide (Aldrich) was dissolved in 5 mL of dimethylformamide (DMF) under argon protection. Subsequently, 0.27 mL of ethyl iodide (Aldrich) and 0.5 mL of 1,8-diazabicyclo[5.4.0]undec-7-ene (Aldrich) were added sequentially and slowly added dropwise.
2. The reaction mixture was stirred at 60 °C for 2 h and then cooled to room temperature. The reaction was terminated by addition of 2N hydrochloric acid solution.
3. The reaction solution was diluted with 20 mL of ethyl acetate and subsequently 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) as eluent to give 518 mg of the target compound (yield: 88%).
4. The above 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.
5. The resulting solid was collected by filtration and 1 mL of 4M dioxane hydrochloride solution (Aldrich) was added to the filtrate, which was filtered and dried to give 263 mg solid (yield: 100%).
6. 10 mg of the resulting solid was dissolved with 44 mg of SAC-0906 in 1 mL of pyridine (Aldrich) under argon protection and stirred at 80 °C for 4 hours.
7. After the reaction solution was cooled to room temperature, it was acidified by adding 2N hydrochloric acid solution and extracted with 20 mL of ether. The organic phase was dried with magnesium sulfate, filtered and concentrated under reduced pressure.
8. The residue was purified by silica gel column chromatography using ethyl acetate/hexane (1:5) as eluent to afford ethoxyamine hydrochloride SAC-1013 (46 mg, yield: 96%).
1H-NMR (300 MHz, CDCl3) δ 5.91-5.76 (m, 2H), 5.34-5.32 (m, 1H), 5.28-5.25 (m, 1H), 5.14 (m, 1H), 4.24-4.10 (m, 3H), 4.04 (q, J = 20.9 Hz, 2H), 3.64-3.48 (m, 1H ), 2.42-0.60 (m, 38H).
