Hydrochloric Acid → 4-Chloro-2,3-dihydro-1H-inden-1-amine--hydrogen chloride (1/1)

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Reaction Steps

A reaction mixture was prepared in a 250 ml. round bottom flask equipped with magnetic stirrer and drying tube containing the following ingredients: 32.5 g. of ammonium acetate, 2.67 g. of sodium cyanoborohydride (NaBH3CN), 70 ml. of tetrahydrofurane (THF), 60 ml. of methanol and 7 g. of 4-chloro-1-indanone. The reaction mixture was stirred at room temperature for about 48 hours. Thin-layer chromatography indicated only a trace of starting ketone remaining. The reaction mixture was cooled to below about 15° C. and acidified to pH = 2 with 12N aqueous hydrochloric acid. Volatile constituents were removed by evaporation in vacuo. The residue was taken up in water and the aqueous mixture extracted three times with ether. The ether extracts were discarded. The aqueous phase was then made basic with 5N aqueous sodium hydroxide and 4-chloro-1-aminoindane, formed in the above reaction, being insoluble in the alkaline layer separated and was extracted into ether. The ether layer was separated and the alkaline layer extracted twice more with ether. The ether extracts were combined, washed with saturated aqueous sodium chloride, and then dried. Evaporation of the ether in vacuo yielded 1.377 g. of an oily residue comprising 4-chloro-1-aminoindane. The hydrochloride salt was prepared by dissolving the residue in ether and passing gaseous hydrogenchloride through the ether solution. The resulting solid hydrochloride salt was separated by filtration. Recrystallization of the salt from a 3:1 isopropanol/ethyl acetate solvent mixture yielded 4-chloro-1-aminoindane hydrochloride melting above 250° C. (total yield = 641 mg.)

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