2-Methoxyphenylacetic acid → (3aRS,4RS,6SR,7aSR)-6-hydroxymethyl-4-(2-fluorophenyl)-2-(2-methoxyphenylacetyl)perhydroisoindol-4-ol

Participants

Reaction Steps

0.066 g of 1-hydroxybenzotriazole and 1.15 g of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride are added to a solution, cooled to 0° C., of 1.48 g of (3aRS,4RS,6SR,7aSR)-6-hydroxymethyl-4-(2-fluorophenyl)perhydroisoindol-4-ol and 0.98 g of 2-methoxyphenylacetic acid in 20 cm3 of dichloromethane. The mixture is stirred at room temperature for 18 hours and then the organic phase is washed with 20 cm3 of water and subsequently with 20 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 2.8 cm, height 20 cm), eluting under a pressure of 0.5 bar of nitrogen with ethyl acetate and collecting fractions of 20 cm3. Fractions 27 to 50 are combined and then concentrated to dryness under reduced pressure (2.7 kPa). 1.33 g of (3aRS,4RS,6SR,7aSR)-6-hydroxymethyl-4-(2-fluorophenyl)-2-(2-methoxyphenylacetyl)perhydroisoindol-4-ol are obtained in the form of a thick white foam.

Provenance & Evidence