Methanol → 1-isopropyl-6-methoxy-1H-indole-4-carboxylic acid methyl ester
Reaction equation
[CH:1]([N:4]1[C:12]2[CH:11]=[C:10]([O:13][CH3:14])[CH:9]=[C:8]([C:15]([OH:17])=[O:16])[C:7]=2[CH:6]=[CH:5]1)([CH3:3])[CH3:2].OS(O)(=O)=O.[CH3:23]O>>[CH3:23][O:16][C:15]([C:8]1[C:7]2[CH:6]=[CH:5][N:4]([CH:1]([CH3:3])[CH3:2])[C:12]=2[CH:11]=[C:10]([O:13][CH3:14])[CH:9]=1)=[O:17]Participants
Procedure
To a stirred suspension of 1-isopropyl-6-methoxy-1H-indole-4-carboxylic acid (700 mg, 3.00 mmol) in MeOH was added H2SO4 (440 mg, 4.50 mmol) and then heated at reflux for 3 h. Methanol was distilled off completely under reduced pressure and the residue basified with saturated aqueous NaHCO3 solution and extracted with ethyl acetate (2×5 mL). The combined organic layers were dried over anhyrous Na2SO4, filtered and concentrated. The residue was purified by column chromatography (SiO2, 100-200) by eluting 5% ethyl acetate in petroleum ether to afford 1-isopropyl-6-methoxy-1H-indole-4-carboxylic acid methyl ester (240 mg, 32.4%) as white solid. 1H NMR (400 MHz, DMSO-d6): δ 1.45 (d, J=6.8 Hz, 6H), 3.84 (s, 3H), 3.88 (s, 3H), 4.81-4.78 (m, 1H), 6.86 (d, J=3.2 Hz, 1H), 7.34 (d, J=2.4 Hz, 1H), 7.39 (d, J=2 Hz, 1H), 7.54 (d, J=3.6 Hz, 1H). LCMS (ES+): m/z=248.16 [M+H].
Workup
- temperatureheated
- temperatureat reflux for 3 h
- distillationMethanol was distilled off completely under reduced pressure
- extractionextracted with ethyl acetate (2×5 mL)
- dry with materialThe combined organic layers were dried over anhyrous Na2SO4
- filtrationfiltered
- concentrationconcentrated
- customThe residue was purified by column chromatography (SiO2, 100-200)
- washby eluting 5% ethyl acetate in petroleum ether
Sources & evidence
- ORD record
- ord-3d1cccb82599438084fc92767e931073
- Source dataset
- uspto-grants-2013_09
- Patent number
- US08536179B2
Reaction notes
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