Synthesis
Step-4: Synthesis of tert-butyl 2-(hydroxymethyl)-1,4-oxoazepane-4-carboxylate
To a dichloromethane solution of (1,4-oxoazepan-2-yl)methanol (550 mg, 4.2 mmol) was added triethylamine (1.2 mL, 8.4 mmol) and di-tert-butyl dicarbonate (1.1 equiv., 1 mL, 4.61 mmol) sequentially at 0°C. The reaction mixture was stirred at room temperature overnight. After completion of the reaction, the reaction was quenched with saturated NaHCO3 solution and then extracted with ethyl acetate. The organic layer was washed sequentially with water and brine, dried over anhydrous Na2SO4 and concentrated to give the target product tert-butyl 2-(hydroxymethyl)-1,4-oxoazepane-4-carboxylate (800 mg, 82.6% yield).
1H NMR (400 MHz, DMSO-d6) δ: 4.68 (m, 1H), 3.95 (m, 1H), 3.70 (m, 1H), 3.54-2.98 (m, 6H), 1.74 (m, 2H), 1.46 (m, 1H), 1.39 (s, 4H).
References
[1] Patent: US2010/168080, 2010, A1. Location in patent: Page/Page column 89
[2] Journal of Medicinal Chemistry, 2017, vol. 60, # 6, p. 2227 - 2244
