Acetic Acid → 4-(3-Isopropyl-1H-indol-5-yloxy)-3,5-bis-trifluoromethylphenylacetic acid
Reaction equation
S(=O)(=O)(O)O.O.[CH:7]([C:10]1[C:18]2[C:13](=[CH:14][CH:15]=[C:16]([O:19][C:20]3[C:25]([C:26]([F:29])([F:28])[F:27])=[CH:24][C:23](CC#N)=[CH:22][C:21]=3[C:33]([F:36])([F:35])[F:34])[CH:17]=2)[NH:12][CH:11]=1)([CH3:9])[CH3:8].C(OCC)(=O)C.[C:43]([OH:46])(=[O:45])[CH3:44]>>[CH:7]([C:10]1[C:18]2[C:13](=[CH:14][CH:15]=[C:16]([O:19][C:20]3[C:25]([C:26]([F:27])([F:29])[F:28])=[CH:24][C:23]([CH2:44][C:43]([OH:46])=[O:45])=[CH:22][C:21]=3[C:33]([F:36])([F:34])[F:35])[CH:17]=2)[NH:12][CH:11]=1)([CH3:9])[CH3:8]Participants
6
Conditions
- Temperature
- 105 °C
Procedure
A mixture of 5 ml of concentrated sulphuric acid and 5 ml of water is added dropwise to a solution of 0.35 g (0.82 mmol) of nitrile derivative from Example VIII in 5 ml of acetic acid (100% strength). The reaction solution is stirred at 105° C. for 4 hours, then cooled to room temperature and treated with ice-cold water and ethyl acetate. The organic phase is separated off, the aqueous solution is extracted again with ethyl acetate, and the combined organic phases are dried over sodium sulphate, filtered and concentrated to give an oil. The crude product (120.3 mg) is chromatographed on silica gel 60 by means of methylene chloride/methanol (95:5 and95:11).
Workup
- temperaturecooled to room temperature
- customThe organic phase is separated off
- extractionthe aqueous solution is extracted again with ethyl acetate
- dry with materialthe combined organic phases are dried over sodium sulphate
- filtrationfiltered
- concentrationconcentrated
- customto give an oil
- customThe crude product (120.3 mg) is chromatographed on silica gel 60 by means of methylene chloride/methanol (95:5 and95:11)
Sources & evidence
- ORD record
- ord-59ff1b95ad6f4c5a8d53ad9d8f698187
- Source dataset
- uspto-grants-2004_09
- Patent number
- US06794406B2
Reaction notes
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