4-(Trifluoromethoxy)-1H-indole-2-carboxylic acid → HCID 53418161, compound

HRID 2278653Notes

Reaction equation

HRID 2278653 reaction equation
[F:1][C:2]([F:17])([F:16])[O:3][C:4]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:5]=1[CH:6]=[C:7](C(O)=O)[NH:8]2>N1C2C(=CC=CC=2)C=CC=1.[Cu]>[F:17][C:2]([F:1])([F:16])[O:3][C:4]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:5]=1[CH:6]=[CH:7][NH:8]2

Participants

4

Reactant 1

HCID 167692654-(Trifluoromethoxy)-1H-indole-2-carboxylic acid

Product 1

HCID 53418161HCID 53418161, compoundYield 40.2%

Reagents, catalysts & solvents 2

HCID 23978CopperCatalystHCID 7047QuinolineSolvent

Conditions

Temperature
200 °C

Procedure

0.18 g of copper(0) is added to a solution of 1.0 g of 4-(trifluoromethoxy)-1H-indole-2-carboxylic acid in 4.5 ml of quinoline under argon. The reaction mixture is heated at 200° C. for 5 hours, and is then cooled to ambient temperature. After dilution with 30 ml of diethyl ether, the mixture is filtered through Clarcel®. The filtrate is washed successively with 6×10 ml of a 6N hydrochloric acid solution, with 10 ml of a saturated sodium hydrogen carbonate solution and then with 10 ml of saturated brine. The organic phase is dried over anhydrous magnesium sulfate, filtered, and then concentrated to dryness under reduced pressure. The residue is purified by chromatography on a 25 g cartridge of 15-40 μm silica, elution being carried out with a 95/5 v/v cyclohexane/ethyl acetate mixture, at a flow rate of 20 ml/min. 0.33 g of 4-(Trifluoromethoxy)indole is thus obtained in the form of an amber oil, the characteristics of which are the following:

Workup

  1. temperatureis then cooled to ambient temperature
  2. filtrationAfter dilution with 30 ml of diethyl ether, the mixture is filtered through Clarcel®
  3. washThe filtrate is washed successively with 6×10 ml of a 6N hydrochloric acid solution, with 10 ml of a saturated sodium hydrogen carbonate solution
  4. dry with materialThe organic phase is dried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated to dryness under reduced pressure
  7. customThe residue is purified by chromatography on a 25 g cartridge of 15-40 μm silica, elution

Sources & evidence

ORD record
ord-afcb6154a16a4ed684cc02c7d8e666c7
Source dataset
uspto-grants-2015_09
Patent number
US09133168B2

Reaction notes

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