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

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.

1. concentrationThe reaction mixture was concentrated under reduced pressure
2. additionTo the solution, methylene chloride (1 ml) and triethylamine (1 ml) were added
3. stirringby stirring at room temperature for 5 minutes
4. concentrationThe solution was concentrated under reduced pressure
5. dissolutionthe residue was dissolved in methanol (10 ml)
6. temperaturewith cooling on ice-bath
7. stirringby stirring at room temperature overnight
8. stirringby stirring
9. dry with materialThe organic phase was dried over magnesium sulfate
10. filtrationfiltered
11. concentrationThe resulting filtrate was concentrated under reduced pressure
12. customThe residue was purified by silica gel column chromatography (methylene chloride/methanol=50/1)
13. customcrystallized from methylene chloride-diisopropyl ether

ORD record

ord-84714c1ef662435c95fba7f383b91500

Source dataset

uspto-grants-2007_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07262212B2