Diphosgene → Formate

Participants

Reaction Steps

A solution of [(1S)-2-(3,5-dichloro-1-oxido-pyridin-1-ium-4-yl)-1-(3,4-dimethoxyphenyl)ethyl]5-[(2-fluoroanilino)methyl]thiophene-2-carboxylate (177 mg, 0.306 mmol) in acetonitrile (6 mL) was added with diphosgene (75 μL, 0.61 mmol) and the reaction mixture was stirred at room temperature for 5 minutes. After which time, a solution of diisopropylethylamine (341 μl, 2.0 mmol) and (R)-1-methylpyrrolidin-3-ol (220 μl, 2.0 mmol) in acetonitrile (3 mL) was added over 10 minutes. The brown mixture was stirred at room temperature for 1 h and then the solvent was removed in vacuo. The crude product was dissolved in chloroform (70 mL) and the organic layer was washed with HCl 1M (50 mL). The organic layer was dried over sodium sulfate and evaporated under vacuum. The crude material was purified by flash chromatography (on a reverse phase C18 60 g column). The collected fractions were evaporated under vacuum and the product was further purified by means of preparative HPLC (Fraction Lynx). The collected fractions were evaporated in vacuo at 45° C. The residue was treated with acetone and diethyl ether to give the title compound as a formate salt as a foam (32 mg, 15%).

Provenance & Evidence