Sodium hydride → 2-(4-Tert-butoxycarbonylpiperazin-1-yl)methyl-2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazole

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Reaction Conditions

Reaction Steps

A solution of 1-(2-methyl-oxiranylmethyl)-4-nitro-1H-imidazole (1.5 g, 5.72 mmol) and piperazine-1-carboxylic acid tert-butyl ester (1.1 g, 5.72 mmol) is dissolved in IPA and heated to 60° C. for 24 h. The solution is concentrated and partitioned between water and ethyl acetate. The organic layer is dried over sodium sulfate and concentrated. The resulting solution of 4-[3-(2-bromo-4-nitro-imidazol-1-yl)-2-hydroxy-2-methyl-propyl]-piperazine-1-carboxylic acid tert-butyl ester (1.1 g, 2.46 mmol) in DMF (15 ml) was treated with sodium hydride (148 mg, 3.69 mmol) and stirred for 3 h at 60° C. The mixture was diluted with water and extracted with ethyl acetate. The organic layer is dried over sodium sulfate and concentrated. The residue is purified by silica gel chromatography to give 4-(2-methyl-6-nitro-2,3-dihydro-imidazo[2,1-b]oxazol-2-ylmethyl)-piperazine-1-carboxylic acid tert-butyl ester (453 mg, 50%) of as a light yellow oil. ESI MS m/z 367 (M+Na+); 1H NMR (400 MHz, CDCl3) δ 7.54 (s, 1H), 4.30 (d, J=10 Hz, 1H), 3.92 (d, J=10 Hz, 1H), 3.45-3.02 (m, 4H), 2.86 (d, J=14.8 Hz, 1H), 2.70-2.39 (m, 4H), 2.55 (d, J=14.8, 1H), 1.58 (s, 3H), 1.45 (s, 9H).

Provenance & Evidence