Trifluoroacetic acid → (2-Methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-yl)methanol

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Reaction Steps

Trifluoroacetic acid (25.4 mL, 0.342 mol) was added dropwise to a stirred mixture of 2-({[4-(benzyloxy)benzyl]oxy}methyl)-2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b][1,3]oxazole (26) (see Example 2Z) (2.53 g, 6.40 mmol) and anisole (7.0 mL, 64 mmol) in CH2Cl2 (100 mL) (water bath cooling). After stirring at room temperature for 4 h, the solvents were removed by blowing under a stream of N2. The oily residue was treated with excess solid NaHCO3, then diluted with 15% MeOH/CH2Cl2 (100 mL), and the mixture was stirred at room temperature for 30 min and then filtered. The filtrate was evaporated to dryness and the residue was chromatographed on silica gel. Elution with 0-1% MeOH/CH2Cl2 firstly gave foreruns, and then further elution with 1-2% MeOH/CH2Cl2 gave (2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b][1,3]oxazol-2-yl)methanol (101) (reported by Tsubouchi et al., WO 2004033463A1 via 3 steps, starting from 2-chloro-4(5)-nitroimidazole (81) and 2-[methoxymethoxy)methyl]-2-methyloxirane) (1.215 g, 95%) as a cream solid: mp (MeOH/CH2Cl2/hexane) 174-176° C.; 1H NMR [(CD3)2SO] δ 8.09 (s, 1H), 5.41 (t, J=5.7 Hz, 1H), 4.24 (d, J=10.6 Hz, 1H), 4.03 (d, J=10.7 Hz, 1H), 3.64 (dd, J=12.2, 5.6 Hz, 1H), 3.54 (dd, J=12.2, 5.9 Hz, 1H), 1.51 (s, 3H). Anal. (C7H9N3O4) C, H, N.

Provenance & Evidence