反应详情

温度

50 °C

To a mixture of 1-[(1R,2R)-2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-3-[4-(1H-tetrazol-1-yl)phenyl]-2-imidazolidinone (0.5 g) and acetonitrile (10 ml) was added iodomethyl (2,3,4,5-tetrahydrofurfuryl) carbonate (0.594 g), and the mixture was stirred for 15 hours at 50° C. The reaction mixture was subjected to silica gel flush chromatography (eluent: ethyl acetate→acetone→acetone/ethanol=10/1), and the fraction containing the desired compound was concentrated under reduced pressure. The residue was subjected to ODS column chromatography (eluent: methanol/water=3/2). The fraction containing the desired compound was concentrated and the residue was lyophilized to give 1-[(2R,3R)-2-(2,4-difluorophenyl)-2-hydroxy-3-[2-oxo-3-[4-(1H-tetrazol-1-yl)phenyl]-1-imidazolidinyl]butyl]-4-[(2,3,4,5-tetrahydrofurfuryl)oxycarbonyloxymethyl]-1H-1,2,4-triazolium iodide (Compound 30, 0.4 g) as a colorless powder. The product was dissolved in water (15 ml), and the solution was subjected to ion-exchange resin [Dowex 1×8 (Cl− type)]. The fraction containing the desired compound was concentrated under reduced pressure, and lyophilized to give 1-[(2R,3R)-2-(2,4-difluorophenyl)-2-hydroxy-3-[2-oxo-3-[4-(1H-tetrazol-1-yl)phenyl]-1-imidazolidinyl]butyl]-4-[(2,3,4,5-tetrahydrofurfuryl)oxycarbonyloxymethyl]-1H-1,2,4-triazolium chloride (Compound 21, 0.24 g) as a colorless powder.

1. customflush chromatography (eluent: ethyl acetate→acetone→acetone/ethanol=10/1)
2. additionthe fraction containing the desired compound
3. concentrationwas concentrated under reduced pressure
4. additionThe fraction containing the desired compound
5. concentrationwas concentrated