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
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]+.
Workup
- concentrationThe reaction mixture was concentrated in vacuo to dryness
- additionThe residue was diluted with water and ethyl acetate
- customThe organic layer was separated
- customdried
- filtrationfiltered
- concentrationconcentrated in vacuo
- customThe crude product was purified by silica gel chromatography (eluent: 8% EtOAC in pet. ether)
Sources & evidence
- ORD record
- ord-244094a92ec34c8f8c51ef1b9d878730
- Source dataset
- uspto-grants-2014_07
- Patent number
- US08765792B2
Reaction notes
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