Water → 7-Chloro-1H-indole-3-carboxylic acid
Reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[NH:9][CH:8]=[CH:7]2.FC(F)(F)[C:13]([O:15]C(=O)C(F)(F)F)=[O:14].O>CN(C)C=O>[Cl:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[NH:9][CH:8]=[C:7]2[C:13]([OH:15])=[O:14]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 7.5 °C
Procedure
A solution of 7-chloroindole (7.1 g, 47.0 mmol) in dimethylformamide (60 ml) was cooled to 5° C. under nitrogen and trifluoroacetic anhydride (7.6 ml, 54.0 mmol) was added over 10 mins, maintaining the temperature below 10° C. The mixture was stirred at 5-10° C. for 2 h, then poured into water (600 ml). The resulting suspension was stirred for 15 mins and the 7-chloro-3-[(trifluoromethyl)carbonyl]-1H-indole precipitate was filtered off, washing with water to neutrality. The damp solid was suspended in 4 M aqueous sodium hydroxide (500 ml) and heated to reflux with stirring for 1 h. The mixture was cooled and washed with diethyl ether (2×100 ml). The aqueous phase was then acidified to pH 1 using 5 M hydrochloric acid and the resulting fine precipitate filtered off, washed with water to neutrality and dried to afford 7-chloro-1H-indole-3-carboxylic acid as a pink solid (7.5 g, 38.0 mmol).
Workup
- temperaturemaintaining the temperature below 10° C
- stirringThe resulting suspension was stirred for 15 mins
- filtrationthe 7-chloro-3-[(trifluoromethyl)carbonyl]-1H-indole precipitate was filtered off
- washwashing with water to neutrality
- temperatureheated
- temperatureto reflux
- stirringwith stirring for 1 h
- temperatureThe mixture was cooled
- washwashed with diethyl ether (2×100 ml)
- filtrationthe resulting fine precipitate filtered off
- washwashed with water to neutrality
- customdried
Sources & evidence
- ORD record
- ord-bdc1915d27db4d8cac24b32dda0ca825
- Source dataset
- uspto-grants-2010_02
- Patent number
- US07655645B2
Reaction notes
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