Trifluoroacetic acid → 2-[4-(4-Trifluoromethylbenzyl)piperazin-1-yl]ethanone

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Reaction Steps

Tert-butyl 4-[2-(2,3-dihydro-6-nitrospiro[imidazo[2,1-b]oxazole-2,4′-piperidine]-1′-yl)-2-oxoethyl]piperazine-1-carboxylate prepared in Example 653 (300 mg, 0.67 mmol) was dissolved in methylene chloride (5 ml). To the solution, trifluoroacetic acid (10 ml) was added followed by stirring at room temperature for 6 hours. The reaction mixture was concentrated under reduced pressure. To the solution, methylene chloride (1 ml) and triethylamine (1 ml) were added followed by stirring at room temperature for 5 minutes. The solution was concentrated under reduced pressure and the residue was dissolved in methanol (10 ml). To the solution, 4-trifluoromethylbenzaldehyde (0.23 ml, 1.67 mmol), sodium cyanotrihydroborate (105 mg, 1.67 mmol) and acetic acid (0.1 ml) were added with cooling on ice-bath followed by stirring at room temperature overnight. To the solution, a saturated aqueous sodium hydrogencarbonate solution and methylene chloride were added followed by stirring. The organic phase was dried over magnesium sulfate and then filtered. The resulting filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (methylene chloride/methanol=50/1) and crystallized from methylene chloride-diisopropyl ether to afford 1-(2,3-dihydro-6-nitrospiro[imidazo[2,1-b]oxazole-2,4′-piperidin])-1′-yl)-2-[4-(4-trifluoromethylbenzyl)piperazin-1-yl]ethanone (226 mg, yield 67%) as a white powder.

Provenance & Evidence