Diisopropylethylamine → (3S,4S)-tert-butyl 4-((6-bromo-7-fluoro-3-nitroquinolin-4-yl)amino)-3-fluoropiperidine-1-carboxylate

Participants

Reaction Steps

6-Bromo-4-chloro-7-fluoro-3-nitroquinoline (17.5 g, 0.0057 mol) was taken in dry DMF (200 mL) under N2 atmosphere. DIPEA (14.8 g, 0.114 mol) and (3S,4S)-tert-butyl 4-amino-3-fluoropiperidine-1-carboxylate (12.5 g, 0.057 mol) in dry DMF (50 mL) was added sequentially at RT. The resulting mixture was stirred for overnight at RT. The reaction was monitored by TLC (30% EtOAc/Hexane), after completion of reaction, the reaction mixture poured into ice water and extracted with EtOAc (3×200 mL). The combined EtOAc layers were washed with brine solution and water, dried over sodium sulphate. The organic layer was evaporated under vacuum and the residue was purified by column chromatography on silica gel (10-50% EtOAc-Hexane) to afford the (3S,4S)-tert-butyl 4-((6-bromo-7-fluoro-3-nitroquinolin-4-yl)amino)-3-fluoropiperidine-1-carboxylate, 1 (27 g, 956% yield). 1HNMR (CDCl3, 400 MHz): δ 9.37 (s, 1H) 8.83-8.81 (d, 1H) 8.48-8.46 (d, 1H) 7.74-7.71 (d, 1H), 4-58-4.40 (m, 2H), 4.19-4.12 (m, 2H), 2.95-2.87 (m, 2H) 2.27-2.23 (m, 1H) 1.79-1.66 (m, 1H), 1.47 (s, 9H); LCMS: 98.84%, (M+2) 488.7; HPLC: 99.47%.

Provenance & Evidence