Citric Acid → N-Butyloxycarbonyl-3-[3-(2-benzoimidazol-1-ylacetyl)phenyl]-5-iso-butyl-thiophene-2-sulfonamide

Participants

Reaction Steps

To a solution of 3-[3-(2-benzoimidazol-1-ylacetyl)phenyl]-5-iso-butyl-N-tert-butylthiophene-2-sulfonamide (54.4 mg, 0.107 mmol; see step (b)) in TFA (3 mL) was added anisole (150 μL) and the reaction mixture was stirred for 28 h at ambient temperature. The reaction mixture was concentrated in vacuo and dried in vacuo overnight. To the crude product dissolved in pyridine (1.5 mL) was added pyrrolidinopyridine (31.6 mg, 0.214 mmol) and butyl chloroformate (135.7 μL, 1.07 mmol), and the reaction mixture was stirred overnight. Another portion of pyrrolidinopyridine (31.6 mg, 0.214 mmol) and butyl chloroformate (135.7 μL, 1.07 mmol) was added and the reaction mixture was stirred overnight. Citric acid (10 mL, 10% aq) was added to the reaction mixture, which was then extracted with EtOAc, dried (over anhydrous MgSO4), concentrated in vacuo, and the residue purified by flash chromatography using MeOH:CH2Cl2 (5:95) as eluent to give the title compound in 36% yield, over two steps, (21 mg, 0.038 mmol).

Provenance & Evidence