3.5%; 77% |
In neat (no solvent); at 120℃; for 2h; |
A solution of commercially available <strong>[446-09-3]2-bromo-5-fluoronitrobenzene</strong> (1.78 g, 8.09 mmol) and morpholine (2.12 mL, 24.3 mmol) was heated for 2 h at 120 C using a Biotage Initiator microwave. The mixture was dissolved in dichloromethane (50 mL) and water (20 mL). The organic phase was separated, dried over Na2S04, filtered and the solvents were removed under reduced pressure. The residue was purified by chromatography on HP-Sil SNAP cartridges using a Biotage Isolera system employing an ethyl acetate/n-heptane gradient (5/95->40/60) to afford the less polar title compound as a bright orange oil which became a solid by standing at room temperature (1.41 g, 77 %). The more polar by-product was isolated as a yellow solid (0.064 g, 3.5 %). Less polar title compound: 1H-NMR (400 MHz, CDCI3): delta = 3.00-3.04 (m, 4H), 3.82-3.86 (m, 4H), 7.18-7.22 (m, 1 H), 7.25-7.30 (m, 1 H), 7.53 (dd, 1 H) More polar by-product: 1H-NMR (400 MHz, CDCI3): delta = 3.18-3.22 (m, 4H), 3.86-3.90 (m, 4H), 6.93 (dd, 1 H), 7.31 (d, 1 H), 7.55 (d, 1 H) |
3.5%; 77% |
at 120℃; for 2h; |
(0677) Step A (0678) A solution of commercially available <strong>[446-09-3]2-bromo-5-fluoronitrobenzene</strong> (1.78 g, 8.09 mmol) and morpholine (2.12 mL, 24.3 mmol) was heated for 2 h at 120 C. using a Biotage Initiator microwave. The mixture was dissolved in dichloromethane (50 mL) and water (20 mL). The organic phase was separated, dried over Na2SO4, filtered and the solvents were removed under reduced pressure. The residue was purified by chromatography on HP-Sil SNAP cartridges using a Biotage Isolera system employing an ethyl acetate/n-heptane gradient (5/95->40/60) to afford the less polar title compound as a bright orange oil which became a solid by standing at room temperature (1.41 g, 77%). The more polar by-product was isolated as a yellow solid (0.064 g, 3.5%). (0679) Less polar title compound: 1H-NMR (400 MHz, CDCl3): delta=3.00-3.04 (m, 4H), 3.82-3.86 (m, 4H), 7.18-7.22 (m, 1H), 7.25-7.30 (m, 1H), 7.53 (dd, 1H). (0680) More polar by-product: 1H-NMR (400 MHz, CDCl3): delta=3.18-3.22 (m, 4H), 3.86-3.90 (m, 4H), 6.93 (dd, 1H), 7.31 (d, 1H), 7.55 (d, 1H). |