1-Hydroxybenzotriazole → (3aS,4S,7aS)-7,7-diphenyl-4-(2-methoxyphenyl)-2-[(S)-2-acetyloxy-2-phenylacetyl]perhydroisoindol-4-ol

Participants

Reaction Steps

0.024 g of 1-hydroxybenzotriazole and 0.33 g of (S)-2-acetyloxy-2-phenylacetic acid are added to a suspension of 0.75 g of (3aS,4S,7aS)-7,7-diphenyl-4-(2-methoxyphenyl)perhydroisoindol-4-ol hydrochloride in 60 cm3 of dry dichloromethane, this solution is then cooled to +5° C. and a suspension of 0.4 g of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride in 20 cm3 of dry dichloromethane is quickly added, followed by a solution of 0.63 cm3 of diisopropylethylamine in 20 cm3 of dry dichloromethane. The reaction mixture is stirred at +5° C. for 2 hours and at room temperature for 24 hours, diluted with 120 cm3 of dichloromethane, washed with 100 cm3 of water and then with 100 cm3 of an aqueous saturated solution of sodium chloride, and is dried over magnesium sulphate and concentrated to dryness under reduced pressure (2.7 kPa). The residue is chromatographed on a Merck silica gel column (particle size 0.04-0.06 mm, diameter 2.5 cm, height 39 cm) by eluting under a pressure of 0.5 bar of nitrogen with a mixture of cyclohexane and ethyl acetate (50/50 by volume) and collecting fractions of 60 cm3. Fractions 6 to 10 are combined and then concentrated to dryness under reduced pressure (2.7 kPa). 0.96 g of (3aS,4S,7aS)-7,7-diphenyl-4-(2-methoxyphenyl)-2-[(S)-2-acetyloxy-2 -phenylacetyl]perhydroisoindol-4-ol is obtained in the form of a white foam.

Provenance & Evidence