Hydrochloric Acid → 4-fluoro-2-methyl-2,3-dihydro-1H-indole

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Reaction Steps

8 ml of concentrated hydrochloric acid are added to a solution of 1.66 g of (R)-2-benzyloxy-1-(4-fluoro-2-methyl-2,3-dihydroindol-1-yl)propan-1-one diastereoisomer (A) in 200 ml of absolute ethanol. The reaction mixture is refluxed with stirring for 40 hours and is then cooled to ambient temperature and concentrated to dryness under reduced pressure. The residue is taken up in 250 ml of water, alkalinized with concentrated sodium hydroxide to pH 14, and then the mixture is extracted with 3×200 ml of dichloromethane. The organic phases are combined, washed with water, dried over magnesium sulfate, filtered, and then concentrated to dryness under reduced pressure. The residue is purified by chromatography on a 70 g cartridge of 15-40 μm silica, elution being carried out with pure heptane and then with a 95/5 heptane/ethyl acetate mixture at a flow rate of 50 ml/min, and then on a 70 g cartridge of 15-40 μm silica, elution being carried out with pure cyclohexane and then with a 70/30 cyclohexane/dichloromethane mixture, at a flow rate of 50 ml/min. 0.50 g of (+)-4-fluoro-2-methylindoline is thus obtained in the form of a colorless oil, the characteristics of which are the following:

Provenance & Evidence