反应详情

温度

0 °C

0.54 g of carbonyldiimidazole is added to a solution of 0.8 g of 2-benzyloxyphenylacetic acid in 10 cm3 of dichloromethane, cooled to 0° C. The mixture is stirred at this temperature for 2 hours and then 0.8 g of (3aRS,4RS,6SR,7aSR)-6-hydroxymethyl-4-(2-fluorophenyl)perhydroisoindol-4-ol hydrochloride and 1.04 cm3 of diisopropylethylamine are added. The reaction mixture is stirred at room temperature for 18 hours, and then the organic phase is washed with 10 cm3 of water, then with 10 cm3 of saturated aqueous sodium chloride solution, dried over magnesium sulphate and concentrated to dryness under reduced pressure (2.7 kPa). The residue is chromatographed on a silica gel column (particle size 0.04-0.06 mm, diameter 3.2 cm, height 20 cm), eluting under a pressure of 0.5 bar of nitrogen with ethyl acetate and collecting fractions of 25 cm3. Fractions 18 to 50 are combined and then concentrated to dryness under reduced pressure (2.7 kPa). 0.72 g of (3aRS,4RS,6SR,7aSR)-6-hydroxymethyl-4-(2-fluorophenyl)-2-(benzyloxyphenylacetyl)perhydroisoindol-4-ol is obtained in the form of a thick white foam.

1. stirringThe reaction mixture is stirred at room temperature for 18 hours
2. washthe organic phase is washed with 10 cm3 of water
3. dry with materialwith 10 cm3 of saturated aqueous sodium chloride solution, dried over magnesium sulphate
4. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
5. customThe residue is chromatographed on a silica gel column (particle size 0.04-0.06 mm, diameter 3.2 cm, height 20 cm)
6. washeluting under a pressure of 0.5 bar of nitrogen with ethyl acetate
7. customcollecting fractions of 25 cm3
8. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)