Hydrazine hydrate (1:1) → 2-(2-{[6-(4-Fluorophenyl)-2-naphthyl]sulfonyl}phenyl)-1,3,4-oxadiazole

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Reaction Steps

Hydrazine hydrate (2.25 mL, 46 mmol) was added to a solution of methyl 2-{[6-(4-fluorophenyl)-2-naphthyl]sulfonyl}benzoate (Example 38, 0.42 g, 1.0 mmol) in 1,4-dioxane (1 mL), stirred for 1 hour at room temperature then heated at 90° C. overnight. Solvent was removed in vacuo and the residue azeotroped using toluene. Triethyl orthoformate (10 mL) and a catalytic quantity of (±)-10-camphorsulfonic acid were added to the resultant crude hydrazide then stirred and heated at 90° C. overnight. Solvent was removed in vacuo, water (100 mL) added and extracted with ethyl acetate (2×75 mL). Extracts were washed with water and saturated brine then dried (MgSO4), filtered and evaporated to a yellow residue. Purification by flash column chromatography eluting with a 20-60% ethyl acetate/isohexane gradient gave 2-(2-{[6-(4-fluorophenyl)-2-naphthyl]sulfonyl}phenyl)-1,3,4-oxadiazole (0.22 g, 51%). 1H NMR (500 MHz, d6-DMSO) δ 9.46 (1H, s), 8.59 (1H, s), 8.40 (1H, dd, J=1.0, 8.0 Hz), 8.37 (1H, s), 8.30 (1H, d, J=8.7 Hz), 8.20 (1H, d, J=8.8 Hz), 8.05 (1H, dd, J=1.7, 8.6 Hz), 8.00-7.96 (1H, m), 7.93-7.91 (3H, m), 7.87-7.85 (2H, m), 7.42-7.33 (2H, m); m/z (ES+) 431 [MH+].

Provenance & Evidence