Sodium Hydroxide → (6-Fluorochroman-3-YL)methanamine

Participants

Reaction Steps

In an argon atmosphere, a mixture of 0.89 g (6.66 mmol) of aluminium trichloride in 40 ml of absolute diethyl ether is added dropwise while stirring at room temperature to a suspension of 1.52 g (40 mmol) of lithium aluminium hydride in 50 ml of absolute diethyl ether. Subsequently, a solution of 3.5 g (20 mmol) of 3-cyano-6-fluoro-2H-chromene in 50 ml of absolute tetrahydrofuran is added dropwise within a period of 20 minutes to the diethyl ether solution. The reaction mixture is then boiled under reflux for 16 hours. After cooling to room temperature, the reaction mixture is carefully decomposed with 1.52 ml of water, 1.52 ml of sodiumhydroxide solution (15%) and 4.6 ml of water. The resulting precipitate is filtered off with suction and the filtrate is concentrated by evaporation in vacuo. The oily residue is dissolved in diethyl ether and the etheral solution is washed with water and then extracted with 2N hydrochloric acid. The combined hydrochloric acid extracts are rendered alkaline with sodium hydroxide solution (30%) while cooling and extracted with dichloromethane. The combined dichloromethane phases are dried over sodium sulfate and concentrated by evaporation in vacuo, yielding 1.89 g of 3-aminomethyl-6-fluoro-chroman in the form of a light-yellow oil. 3-Aminomethyl-6-fluoro-chroman hydrochloride, prepared therefrom with hydrochloric acid in diethyl ether, crystallizes from methanol/acetone and has a melting range of from 208° to 211°.

Provenance & Evidence