Citric Acid → N-Butyloxycarbonyl-3-(3-pyrrolidine-2,5-dione-1-ylmethylphenyl)-5-iso-butylthiophene-2-sulfonamide

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Reaction Steps

To a solution of 3-(3-pyrrolidine-2,5-dione-1-ylmethylphenyl)-5-iso-butyl-N-tert-butylthiophene-2-sulfonamide (95.0 mg, 0.205 mmol; see step (f)) in CH2Cl2 (2 mL) was added BCl3 (0.6 mL, 1.0 M in hexane) and the reaction mixture was stirred for 1 h at ambient temperature. The reaction mixture was concentrated in vacuo. Water (5 mL) was added to the residue and this was then extracted with EtOAc. The combined organic phase was washed with water and brine, dried (over anhydrous MgSO4) and concentrated in vacuo. To the crude product dissolved in pyridine (1.5 mL) was added pyrrolidinopyridine (91.3 mg, 0.616 mmol) and butyl chloroformate (261.1 μL, 2.05 mmol) and the reaction mixture was stirred overnight. Citric acid (3 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 was purified by LCMS (Liquid Chromatography Mass Spectrum; 25-100% CH3CN in water) to give the title compound in 76% yield, over two steps, (79.1 mg, 0.156 mmol).

Provenance & Evidence