Tetrahydrofuran → tert-Butyl 4-(methoxy(methyl)carbamoyl)piperidine-1-carboxylate

Participants

Reaction Steps

To a 500 ml round bottom flask was added 150 ml tetrahydrofuran and 24.8 g 1-(tert-butoxycarbonyl)piperidine-4-carboxylic acid (108 mmol). Carbonyldiimidazole (CDI) (18.4 g, 114 mmol) was added in portions. The reaction mixture was stirred at room temperature for 1 hour. Methylmehoxy amine hydrochloride salt (14.8 g, 151 mmol) was added followed by 22.6 ml triethylamine. The reaction mixture was heated at 55° C. for 1 hour. It was cooled with ice bath and diluted with 200 ml ether. The resulting mixture was washed sequentially twice with 150 ml of saturated ammonium chloride solution, 150 ml 5% KOH solution and 100 ml brine. The organic layers were dried over sodium sulfate, filtered and concentrated. The residue was dissolved in 50 ml toluene and then reconcentrated under vacuum to give 29 g colorless oil which was used for next step without further purification.

Provenance & Evidence