Dimethylamine → N,N-dimethyl-[5-[4-(phenoxymethyl)benzoyl]-4,5,6,7-tetrahydrofuro[3,2-c]pyridin-2-ylmethyl]amine

Participants

Reaction Steps

To a solution of 0.160 g (1.000 mmol) of 4,5,6,7-tetrahydrofuro[3,2-c]pyridine hydrochloride, 0.251 g (1.1 mmol) of 4-(phenoxymethyl)benzoic acid and 0.55 ml (4.0 mmol) of triethylamine in 30 ml of N,N-dimethylformamide, 0.245 g (1.5 mmol) of diethyl cyanophosphonate was added dropwise under ice-cooling, followed by overnight stirring at room temperature. Water was added, followed by 2 extractions with ethyl acetate. The combined organic layer was washed with water and dried over anhydrous sodium sulfate; the solvent was distilled off under reduced pressure. The resulting crude product was dissolved in 10 ml of acetic acid; 0.135 ml (1.50 mmol) of 50% aqueous dimethylamine and 0.122 ml (1.50 mmol) of 37% aqueous formaldehyde were added, followed by stirring at 100° C. for 90 minutes. After the solvent was distilled off under reduced pressure, the residual solution was alkalified with 5% aqueous sodium hydrogen carbonate, and extracted with ethyl acetate 2 times. The combined organic layer was washed with water and dried over anhydrous sodium sulfate; the solvent was distilled off under reduced pressure. The resulting crude product was purified by silica gel column chromatography (ethyl acetate/methanol=5/1) to yield the desired product.

Provenance & Evidence