Carbon Dioxide → 5-(trifluoromethyl)-1H-indole-7-carboxylic acid
Reaction equation
Br[C:2]1[CH:3]=[C:4]([C:11]([F:14])([F:13])[F:12])[CH:5]=[C:6]2[C:10]=1[NH:9][CH:8]=[CH:7]2.[Li]CCCC.[C:20](=[O:22])=[O:21].O>C1COCC1.CCCCCC>[F:12][C:11]([F:14])([F:13])[C:4]1[CH:5]=[C:6]2[C:10](=[C:2]([C:20]([OH:22])=[O:21])[CH:3]=1)[NH:9][CH:8]=[CH:7]2Participants
Conditions
- Temperature
- 2.5 °C
Procedure
584 mg of 7-bromo-5-trifluoromethyl-indole (2.2 mmol) were dissolved in 15 ml THF and 4.1 ml of a 1.6 molar solution of n-BuLi in hexane were added at −78° C. The reaction mixture was then allowed to warm to 0-5° C. and was stirred at this temperature for 30 min. Then it was cooled again to −78° C., dry ice was added and the mixture was allowed to warm to rt. After 15 min at rt it was poured into water and extracted twice with ether. The aqueous phase was then acidified with 1 N HCl solution and extracted several times with DCM. The combined DCM extracts were then washed with brine, dried with magnesium sulfate, filtered and the solvent was evaporated. The remaining residue was triturated with n-hexane. Final filtration yielded 157 mg (31%) of 5-trifluoromethyl-1H-indole-7-carboxylic acid as an off-white solid. 1H NMR (DMSO-d6, 300 MHz): δ 6.66 (m, 1H), 7.48 (m, 1H), 7.89 (s, 1H), 8.18 (s, 1H), 11.46 (br s, 1H), 13.48 (br s, 1H).
Workup
- temperatureThen it was cooled again to −78° C.
- temperatureto warm to rt
- extractionextracted twice with ether
- extractionextracted several times with DCM
- washThe combined DCM extracts were then washed with brine
- dry with materialdried with magnesium sulfate
- filtrationfiltered
- customthe solvent was evaporated
- customThe remaining residue was triturated with n-hexane
- filtrationFinal filtration
Sources & evidence
- ORD record
- ord-b71269be1a87467c89d86be9847a4ac9
- Source dataset
- uspto-grants-2007_08
- Patent number
- US07259183B2
Reaction notes
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