Dimethylformamide → Methyl 5-bromo-3-isopropyl-1-methyl-1H-indole-7-carboxylate

Reaction equation

[Br:1][C:2]1[CH:3]=[C:4]2C(=[C:9]([C:11]([OH:13])=[O:12])[CH:10]=1)NC=[C:5]2[CH:14]([CH3:16])[CH3:15].I[CH3:18].[H-].[Na+].[CH3:21][N:22]([CH:24]=O)[CH3:23]>>[Br:1][C:2]1[CH:3]=[C:4]2[C:23](=[C:9]([C:11]([O:13][CH3:18])=[O:12])[CH:10]=1)[N:22]([CH3:21])[CH:24]=[C:5]2[CH:14]([CH3:16])[CH3:15]

Participants

Reactant 4

HCID 6228Dimethylformamide

HCID 6328Methyl iodide

HCID 24758Sodium hydride

HCID 678183425-Bromo-3-isopropyl-1H-indole-7-carboxylic acid

Product 1

HCID 67816097Methyl 5-bromo-3-isopropyl-1-methyl-1H-indole-7-carboxylateYield 64%

Procedure

To a stirred solution of 5-bromo-3-(1-methylethyl)-1H-indole-7-carboxylic acid (15 g, 53.2 mmol) in DMF (100 mL) at 0° C. was added iodomethane (13.25 mL, 212.7 mmol) followed by sodium hydride (2.8 g, 122.3 mmol). The reaction mixture was allowed to warm to room temperature and stirred for 2 h. The reaction mixture was concentrated in vacuo to dryness. The residue was diluted with water and ethyl acetate. The organic layer was separated and dried, filtered, and concentrated in vacuo. The crude product was purified by silica gel chromatography (eluent: 8% EtOAC in pet. ether) to afford methyl 5-bromo-1-methyl-3-(1-methylethyl)-1H-indole-7-carboxylate (10.58 g, 64%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.23 (d, 6H, J=6.4 Hz), 3.10-3.19 (m, 1H), 3.74 (s, 3H), 3.92 (s, 3H), 7.22 (s, 1H), 7.58 (s, 1H), 7.95 (s, 1H). MS (ES)+m/e 310.1 [M+H]+.