Imidazole → HCID 178474530, compound

Participants

Reaction Steps

To a stirred solution of the 2-(1-trityl-1H-imidazol-4-yl)phenol (0.5 mmol) in anhydrous DMF (3 mL) at 0° C. was added NaH (36.0 mg, 0.75 mmol). The resulting suspension was allowed to stir for 10 min. To the resulting solution was added 3-(acetamidomethyl)benzyl 4-methylbenzenesulfonate (200.0 mg, 0.6 mmol). After stirring overnight, the reaction mixture was carefully diluted with water and extracted with ethyl acetate (2×10 mL). The combined organic layers were washed with water, brine and dried (Na2SO4). The solvent was removed under reduced pressure and the crude product purified using column chromatography. The product was isolated as white solid in 63% yield. 1H NMR:1.95 (s, 3H), 4.21 (d, 2H, J=6.0 Hz), 4.95 (s, 2H), 5.65 (bis, 1H), 6.91 (d, 1H, J=7.6 Hz), 7.10-7.30 (m, 21H), 7.40-7.46 (m, 3H), 7.60-7.68 (m, 1H), 8.19 (dd, 1H, J=7.6, 1.6 Hz). To a stirred solution of the obtained imidazole (0.25 mmol) in anhydrous DMF (3 mL) at 0° C. was added NaH (18.0 mg, 0.37 mmol). The resulting suspension was allowed to stir for 10 min. To the resulting solution was added benzylbromide (51.0 mg, 0.30 mmol). After stirring overnight, the reaction mixture was carefully diluted with water and extracted with ethyl acetate (2×10 mL). The combined organic layers were washed with water, brine and dried (Na2SO4). The solvent was removed under reduced pressure and the crude product was taken to next step without further purification. To a solution of the crude product obtained above was added acetic acid (1.0 mL) and MeOH (4.0 mL). The solution was stirred at 80° C. for 2 h. The solution was allowed to cool to room temperature and the pH was adjusted to ˜10 with 10% NaOH (aq). The aqueous phase was extracted with EtOAc (3×20 mL). The combined organic layer were washed with water, brine, and dried. The solvent was removed in vacuum to afford the crude residue, which was purified by flash column chromatography on silica gel to afford the desired product (1:1 rotamer) in 35% overall yield. 1H NMR:2.15 (s, 3H), 2.18 (s, 3H), 4.18 (s, 2H), 4.47 (s, 2H), 4.60 (s, 2H), 5.15 (s, 2H), 5.18 (s, 2H), 7.00-7.50 (m, 22H), 7.56 (s, 2H), 7.66 (s, 2H), 7.93 (d, 2H, J=7.6 Hz), 8.07 (d, 2H, J=7.6 Hz)

Provenance & Evidence