Dimethylformamide → 3-(Azidomethyl)-2-(3-fluorophenyl)-8-methoxyquinoline

Participants

Reaction Steps

To a stirring solution of 3-(chloromethyl)-2-(3-fluorophenyl)-8-methoxyquinoline hydrochloride (0.9601 g, 2.839 mmol) in DMF (14.19 mL, 2.839 mmol) was added sodium azide (0.3691 g, 5.678 mmol) at room temperature and the mixture was stirred at room temperature After 1 h, the mixture was partitioned between EtOAc (100 mL) and H2O (100 mL). The organic layer was washed with brine (100 mL×1), dried over Na2SO4, filtered, and concentrated under reduced pressure to give 3-(azidomethyl)-2-(3-fluorophenyl)-8-methoxyquinoline as a yellow solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 8.48 (1H, s), 7.54-7.62 (3 H, m), 7.43-7.49 (2H, m), 7.32-7.39 (1H, m), 7.21-7.28 (1H, m), 4.68 (2H, s), 3.97 (3H, s); LC-MS (ESI) m/z 309.1 [M+H]+. The yellow solid was carried on crude without purification for the next step. To a stirring solution of 3-(azidomethyl)-2-(3-fluorophenyl)-8-methoxyquinoline (0.8163 g, 2.65 mmol) in 12 mL of THF-H2O (4:1) was added dropwise trimethyl-phosphine, 1.0 M solution in THF (3.18 mL, 3.18 mmol) at room temperature and the mixture was stirred at room temperature. After 1.5 h, the mixture was diluted with ice-cold 1 N NaOH (100 mL) and extracted with EtOAc (100 mL×2). The combined organic layers were washed with brine (100 mL×3), dried over Na2SO4, and concentrated under the reduced pressure to give a yellow solid (0.8054 g). The yellow solid (0.8054 g) was purified by column chromatography on a 80 g of Redi-Sep™ column using 0-100% gradient of EtOAc in hexane over 25 min, then 100% isocratic of EtOAc for 10 min, then 0% to 50% gradient of CH2Cl2:MeOH:NH4OH (89:9:1) in CH2Cl2 over 25 min, and then 50% isocratic of CH2Cl2:MeOH:NH4OH (89:9:1) for 10 min as eluent to give (2-(3-fluorophenyl)-8-methoxyquinolin-3-yl)methanamine as a yellow syrupy solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 8.45 (1H, s), 7.44-7.59 (5H, m), 7.28-7.36 (1H, m), 7.13-7.19 (1H, m), 3.95 (3H, s), 3.83 (2H, d, J=0.8 Hz), 1.98 (2H, br. s.); LC-MS (ESI) m/z 283.1 [M+H]+.

Provenance & Evidence