Imidazole → 4-Hydroxy-4-[4-(1H-imidazol-1-yl)phenyl]cyclohexanone

Participants

Reaction Conditions

Reaction Steps

To a solution of imidazole (102 mg, 1.5 mmol) and 8-(4-iodo-phenyl)-1,4-dioxa-spiro[4.5]decan-8-ol (316 mg, 1 mmol) in DMF (1 mL) was added CuI (19 mg, 0.1 mmol) and Cs2CO3 (488 mg, 1.5 mmol) and the mixture was stirred at 190° C. under microwave for 10 min. The mixture was diluted with ethyl acetate (50 mL) and water (10 mL). The organic layer was filtered through celite and the filtrate was washed with saline solution (2×10 mL), dried over sodium sulfate, and concentrated in vacuo. The residue was dissolve in THF (1 mL) and was treated with 5% HCl (9 mL) at rt for 14 h. The mixture was neutralized with 1N NaOH to pH 7, concentrated on rotovap, and then extracted with EtOAc (2×50 mL). The organic extracts were combined, washed with saline solution (2×50 mL), dried over sodium sulfate, concentrated in vacuo. The resulting residue was chromatographed on silica gel, eluting with hexane/ethyl acetate (100/0 to 0/100), to provide the desired compound (180 mg, 70% for the two steps). LCMS: 257.2 (M+H+, 100%); 1H NMR: (CDCl3) δ 7.82 (s, 1H), 7.64 (d, 2H), 7.40 (s, 1H), 7.28 (s, 1H), 7.21 (s, 1H), 2.99-2.91 (m, 2H), 2.43-2.28 (m 4H), 2.23-2.18 (m, 2H).

Provenance & Evidence