Tetrahydrofuran → HCID 178456805, compound

Participants

Reaction Steps

Argon was bubbled through a mixture of (S)-tert-butyl (1-(6-bromo-1-(methoxymethyl)-1H-benzo[d]imidazol-2-yl)propyl)carbamate (Preparation 19, 218 mg, 0.55 mmol), [1,1-bis(diphenylphosphino)ferrocene]dichloropalladium(11) (45.0 mg, 0.0615 mmol), and cyclobutylzinc bromide in tetrahydrofuran (0.5 M, 5.5 mL, 2.8 mmol) for 5 minutes. The mixture was then heated at reflux for 18 hours. After cooling, the reaction was concentrated in vacuo, redissolved in ethyl acetate, and washed with water and brine. The organic layer was dried over anhydrous magnesium sulphate, filtered, and concentrated in vacuo. The residue was purified using silica gel column chromatography eluting with a 0-100% ethyl acetate/hexanes gradient to afford the fully protected intermediate as a brown oil. To this oil, cooled in an ice water bath, was added boron tribromide (0.5 mL, 5 mmol) and the reaction was allowed to warm to room temperature and stirred for 5 days. The resulting mixture was then purified by preparative HPLC to provide the title compound (32 mg, 13%) as a white solid.

Provenance & Evidence