Ammonia → 5-Chloro-6-fluoro-2-methyl-1,2,3,4-tetrahydroquinoline

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Reaction Steps

6-Fluoro-5-acetylamino-1,2,3,4-tetrahydroquinaldine (8 g) was dissolved in a mixture of 35 ml of concentrated hydrochloric acid and 20 ml of water. After refluxing the solution for 1 hour 10 ml of an aqueous solution having dissolved therein 5 g of sodium nitrite was added dropwise to the solution under ice-cooling taking care that the reaction temperature should not exceed 5° C. After completion of the addition the reaction mixture was stirred at the same temperature as above for 1 hour and poured into a solution of 12 ml of concentrated hydrochloric acid and 10 g of cuprous hydrochloride. The mixture was allowed to react at 80° C. for 1 hour and ice-cooled. After rendering it alkaline with an aqueous 28% ammonia solution the reaction mixture was extracted with 300 ml chloroform and Celite (diatomaceous earth, produced by Johns Manville Sales Corp.). The chloroform fraction obtained was dried over anhydrous sodium sulfate and concentrated. The residue was purified through a silica gel column chromatography (silica gel: Wako C-200, a trade name for a product of Wako Junyaku Co., Ltd.; eluent: chloroform-ethanol (9:1 by volume) to obtain 3.2 g of 6-fluoro-5-chloro-1,2,3,4-tetrahydroquinaldine as light orange oily product. Production of this compound was confirmed by NMR spectral analysis and mass spectral analysis.

Provenance & Evidence