Hydrochloric Acid → 3-(2-chloro-4-quinolinyl)-2,5-dimethyl-1H-indole-1-acetic acid

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Reaction Steps

7-chloro-4-(2,5-dimethyl-1H-indol-3-yl)quinoline (370 mg) was dissolved in dry THF (8 ml), and maintained under a nitrogen atmosphere. The reaction was cooled to −5° C. before slowly adding NaH (53 mg, 60% dispersion in mineral oil) portion-wise. Allowed the mixture to warm to RT and stirred for 40 minutes. The mixture was cooled to 0° C. before adding ethyl bromoacetate (0.147 ml) dropwise. After stirring for 1 hour at 15° C., the reaction was diluted with EtOH (5 ml) and 10% aqueous NaOH solution (3 ml). Stirring over night at RT converted the ethyl ester to the acid. Acidified with 1M aqueous HCl and extracted with EtOAc (×3). The combined organics were washed with water and brine then dried (Na2SO4) and the solvent was evaporated under reduced pressure. Further purification was by solid phase extraction using NH2 sorbent (6.5 g), eluting CH3CN and 20% AcOH/CH3CN. The solvent was evaporated under reduced pressure and the residue was azeotroped using toluene. This gave the title compound (378 mg).

Provenance & Evidence