2,4-Difluoronitrobenzene → HCID 178507656, compound

To a solution of 2,4-difluoro-1-nitrobenzene (0.92 mL, 8.36 mmol) in CH3CN (60 mL) were added cis-3-benzyloxycyclobutylamine (1.48 g, 8.36 mmol) and DIPEA (1.46 mL, 8.36 mmol). The reaction mixture was stirred at RT for 18 h then concentrated in vacuo to afford the title compound as yellow oil (3.2 g, quantitative). To a solution of the product thus obtained (1.6 g, 5.03 mmol) in MeOH (20 mL) was added Iron powder (1.13 g, 20.12 mmol), NH4Cl (1.56 g, 30.18 mmol) and H2O (8 mL) and the reaction mixture stirred at 90° C. for 2 h under a nitrogen atmosphere. The resulting dark green mixture was filtered through a pad of Celite® and the filtrate concentrated in vacuo giving a dark brown solid. The crude material was partitioned between EtOAc (50 mL) and water (30 mL). Aqueous layer extracted with EtOAc (2×30 mL). The combined organic fractions were washed with brine (20 mL), dried (MgSO4) and concentrated in vacuo to afford the title compound as a dark brown gum (1.13 g, 78%). 1H NMR (CDCl3, 300 MHz): δ 7.25-7.30 (5H, m), 6.6 (1H, dd, J=14.0, 2.8 Hz), 6.35-6.26 (1H, m), 6.26-6.18 (1H, m), 4.43 (2H, s), 3.95-3.83 (1H, m), 3.50-3.37 (1H, m), 2.90-2.78 (2H, m), 1.92-1.79 (2H, m). NMR: 328138. LCMS (Method B): RT 2.87 min [M+H]+ 287.