Hydrochloric Acid → 3-(1,2,3,6-Tetrahydropyridin-4-yl)-1H-indole

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Reaction Steps

50 ml of aqueous N phosphoric acid and 39.3 g of the hydrochloride of 4-piperidone monohydrate were added under a nitrogen atmosphere to a stirred solution of 10 g of indole in 200 ml of acetic acid heated to 95°-100° C. and the mixture was held at 100° C. for one hour and was then cooled. The mixture was poured into 350 ml of concentrated ammonium hydroxide containing ice and the mixture was extracted with ethyl acetate. The organic extract was washed with water, with aqueous sodium chloride solution and was dried over magnesium sulfate and evaporated to dryness to obtain 14.7 g of raw product. The latter was empasted with 75 ml of methanol under nitrogen and the mixture was vacuum filtered. The recovered product was rinsed with methanol and ether to obtain 1.42 g of 3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole melting at 185°-186° C. The mother liquors were evaporated and the residue was chromatographed over silica gel. Elution with a 6-3-1 chloroform-methanol-triethylamine mixture yielded 4.55 g of product with a Rf=0.15 and the latter was empasted with ether to obtain 4.295 g of the desired product for a total yield of 5.715 g. The latter was crystallized from hot and cold isopropanol to obtain 3.56 g of the product melting at 190°-191° C.

Provenance & Evidence