1,8-Diazabicyclo(5.4.0)undec-7-ene → Ethyl 3-{[1-(biphenyl-4-ylmethyl)-4,6-difluoro-5-iodo-1H-benzimidazol-2-yl]oxy}cyclobutanecarboxylate

Participants

Reaction Conditions

Reaction Steps

To a solution of 1-(biphenyl-4-ylmethyl)-4,6-difluoro-5-iodo-2-(methylsulfonyl)-1H-benzimidazole (Intermediate 5, 0.457 g, 0.872 mmol) and 3-hydroxy-cyclobutanecarboxylic acid ethyl ester (Intermediate 12, 0.503 g, 3.49 mmol) in 2.9 mL of DMF was added DBU (0.526 mL, 3.49 mmol) dropwise via syringe. The reaction was heated at 80° C. for 1 h, and then diluted with EtOAc and H2O. The layers were separated and the aqueous layer was extracted with EtOAc. The combined organic layers were washed with brine, dried over Na2SO4, filtered, and concentrated. The resulting crude residue was purified on silica gel (eluted 2-15% then 15% then 15-20% EtOAc/hexanes: gradient elution) to give the desired product. LCMS: calculated for C27H23F2IN2O3 588.38, observed m/e 588.9 (M+H)+ (Rt 2.55/4 min).

Provenance & Evidence