Trifluoroacetic acid → (S)-2-chloro-1-[4-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethyl)piperazin-1-yl]ethanone

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Reaction Steps

A mixture of tert-butyl (S)-4-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethyl)-piperazine-1-carboxylate prepared in Example 393 (1.5 g, 4.1 mmol) and trifluoroacetic acid (20 ml) was stirred at room temperature for 3 hours. The reaction mixture was concentrated under reduced pressure. The residue was dissolved in methylene chloride (20 ml), and the solution was added triethylamine (3 ml) and 4-dimethylaminopyridine (100 mg, 0.82 mmol) in this order. To the mixture, a solution of chloroacetyl chloride (0.49 ml, 6.2 mmol) in methylene chloride (2 ml) was added slowly with cooling on ice-bath followed by stirring at room temperature overnight. The reaction mixture was washed with water twice, a saturated sodium hydrogencarbonate solution and a saturated saline solution in this order, dried over magnesium sulfate and then filtered. The filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (methylene chloride/methanol=100/1) to afford (S)-2-chloro-1-[4-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethyl)piperazin-1-yl]ethanone (600 mg, yield 43%) as a light brown powder.

Provenance & Evidence