Synthesis
GENERAL STEPS: Lithium aluminum hydride (LiAlH4, 228 mg, 6 mmol) was added batchwise to a stirred tetrahydrofuran (THF, 10 mL) solution of 1,2,3,4-tetrahydroquinoxaline (270 mg, 2 mmol) at 0 °C. The reaction mixture was stirred at 0 °C for 30 min, then brought to room temperature and stirred overnight. Upon completion of the reaction, the reaction was quenched sequentially by the addition of 0.25 mL of water, 0.25 mL of 5N sodium hydroxide solution and 1.25 mL of water. The insoluble material was removed by filtration and the filtrate was extracted with ethyl acetate (EtOAc, 3 x 20 mL). The organic layers were combined, washed with saturated saline, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The crude product was purified by fast column chromatography (eluent: 0-60% ethyl acetate/hexane) to give a light yellow solid (90 mg, 34% yield). The product obtained in the previous step (90 mg, 0.67 mmol) was dissolved in THF at 0 °C and di-tert-butyl dicarbonate (Boc2O, 146 mg, 0.67 mmol) and 1N aqueous sodium hydroxide solution (0.67 mL) were added. The reaction mixture was stirred at room temperature overnight. After completion of the reaction, it was quenched with water and extracted with ethyl acetate (EtOAc, 3 x 10 mL). The organic layers were combined, washed with saturated saline, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude product was purified by fast column chromatography (eluent: 0-60% ethyl acetate/hexane) to afford a light yellow oil (90 mg, 57% yield).1H NMR (400 MHz, CDCl3) δ 7.49 (d, J = 7.7 Hz, 1H), 6.89 (td, J = 8.0,1.4 Hz, 1H), 6.69-6.60 (m, 1H ), 6.55 (dd, J = 8.0,1.3Hz, 1H), 3.94 (s, 1H), 3.83-3.69 (m, 2H), 3.47-3.34 (m, 2H), 1.52 (s, 9H).
References
[1] Patent: WO2017/142883, 2017, A1. Location in patent: Paragraph 0225; 0227
[2] Patent: WO2016/86200, 2016, A1. Location in patent: Page/Page column 230; 231
[3] Patent: EP2172453, 2010, A1. Location in patent: Page/Page column 17
