Propylamine → HCID 54253268, compound

Participants

Reaction Steps

To a stirring solution of 1-(pyridin-4-yl)-2-[3-(trifluoromethyl) phenyl]ethane-1,2-dione 2-oxime (83 mmol, 24.43 g), and 1-benzyloxycarbonyl-piperidine-4-carboxaldehyde [Amici et al Eur. J. Med. Chem. 26, 625-631 (1991)] (108 mmol, 26.7 g) in acetic acid (300 mL) was added propylamine (1.24 mol, 73.6 g) in a dropwise manner at ambient temperature. The reaction was heated to reflux for 3 h, cooled to ambient temperature and basified to pH8 with concentrated ammonium hydroxide/ice and extracted with ethyl acetate (3×500 mL). The combined organic layers were washed with brine dried over anhydrous sodium sulfate and evaporated under reduced pressure. The residue was dissolved in methanol (100 mL) and treated with a solution of titanium trichloride (3×150 mL of 10-20 wt % in 20-30% HCl) and stirred for 18 h. The reaction was basified to pH10 with saturated potassium carbonate and extracted with ethyl acetate (4×300 ml). The organic layers were combined, washed with brine, dried over anhydrous sodium sulfate and evaporated under reduced pressure. The residue was chromatographed on silica, eluting with a gradient of 30%-60% ethyl acetate:hexane to give a yellow oil which was rechromatographed on silica, eluting with a gradient of 25%-50% ethyl acetate:hexane to give 10.8 g of a pale yellow oil.

Provenance & Evidence