Diisopropyl diazene-1,2-dicarboxylate → HCID 59199341, compound

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Reaction Steps

To a solution of 5-fluoro-indan-1-ol (0.293 g, 1.925 mmol) and methyl 4-imidazolecarboxylate (CAS#17325-26-7, 0.163 g, 1.290 mmol) in THF (10 mL) at 0° C. is added pMe2NPhP(Ph)2 (0.619 g, 1.925 mmol) and diisopropyl azodicarboxylate (94%, 0.414 g, 1.925 mmol). After 1 hour the mixture is warmed to room temperature and after 18 hours it is diluted with ethyl acetate and extracted with 1M aqueous HCl. The extracts are cooled to 0° C., and the pH is adjusted to ca. 9 with ice-cold 4M aqueous NaOH. The basic aqueous phase is extracted three times with dichloromethane, and the combined organic phases are dried over magnesium sulfate, filtered through a cotton plug, and concentrated. The resulting residue is purified by silica gel flash chromatography (elution with dichloromethane-methanol, 1:0 to 99:1 to 49:1) to afford 3-(5-fluoro-indan-1-yl)-3H-imidazole-4-carboxylic acid methyl ester; MS: (ESI) m/z 261.0 (M+H)+. The HCl salt of the title compound can be prepared by dissolution in diethyl ether followed by treatment with an excess of 1N HCl in diethyl ether. The resulting heterogeneous solution is concentrated to furnish the HCl salt of 3-(5-fluoro-indan-1-yl)-3H-imidazole-4-carboxylic acid methyl ester; 1H NMR (400 MHz, CDCl3) δ ppm 2.06-2.20 (m, 1 H), 2.71-2.85 (m, 1 H), 2.87-3.00 (m, 1 H), 3.00-3.14 (m, 1 H), 3.87 (s, 3 H), 6.47 (dd, J=7.7, 4.7 Hz, 1 H), 6.88-6.97 (m, 1 H), 7.01 (dd, J=8.6, 2.3 Hz, 1 H), 7.16 (dd, J=8.6, 5.1 Hz, 1 H), 7.19 (s, 1 H), 7.77 (s, 1 H).

Provenance & Evidence