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

Reaction equation

Cl.Cl[CH2:3][C:4]1[C:5]([C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([F:22])[CH:17]=2)=[N:6][C:7]2[C:12]([CH:13]=1)=[CH:11][CH:10]=[CH:9][C:8]=2[O:14][CH3:15].CN(C=O)C.[N-:28]=[N+:29]=[N-:30].[Na+]>>[N:28]([CH2:3][C:4]1[C:5]([C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([F:22])[CH:17]=2)=[N:6][C:7]2[C:12]([CH:13]=1)=[CH:11][CH:10]=[CH:9][C:8]=2[O:14][CH3:15])=[N+:29]=[N-:30]

Participants

Reactant 3

HCID 6228Dimethylformamide

HCID 33557Sodium Azide

HCID 689445683-(Chloromethyl)-2-(3-fluorophenyl)-8-methoxyquinoline hydrochloride

Product 1

HCID 866700723-(Azidomethyl)-2-(3-fluorophenyl)-8-methoxyquinoline

Procedure

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 (1 H, s), 7.54-7.62 (3 H, m), 7.43-7.49 (2 H, m), 7.32-7.39 (1 H, m), 7.21-7.28 (1 H, m), 4.68 (2 H, s), 3.97 (3 H, s); LC-MS (ESI) m/z 309.1 [M+H]+. The yellow solid was carried on crude without purification for the next step.