反应详情

Add N-methylmorpholine (13.0 mL, 118 mmol) to a solution of 1-(tert-butoxycarbonyl)piperidine-4-carboxylic acid (11.2 g, 48.8 mmol) in THF (400 mL) at −10° C. and stir for 5 min. Add isobutyl chloroformate (5.1 mL, 38.8 mmol) and continue stirring at −10° C. for 2 h. Add 2-amino-1-(3-(trifluoromethyl)phenyl)ethanone hydrochloride (9.35 g, 39.0 mmol) and continue stirring for 1 h. Add methylene chloride (500 mL) to the mixture and filter. Wash the filtrate with sat. aqueous sodium bicarbonate (400 mL) and concentrate in vacuo. Purify the residue by silica gel chromatography (330 g RediSep column, eluting with a gradient of 0% to 100% ethyl acetate:hexane, 6.0 L) to provide tert-butyl 4-(2-oxo-2-(3-(trifluoromethyl)phenyl)ethylcarbamoyl)piperidine-1-carboxylate (9.72 g, 60%).

1. filtrationAdd methylene chloride (500 mL) to the mixture and filter
2. washWash the filtrate with sat. aqueous sodium bicarbonate (400 mL)
3. concentrationconcentrate in vacuo
4. customPurify the residue by silica gel chromatography (330 g RediSep column
5. washeluting with a gradient of 0% to 100% ethyl acetate