4-Toluenesulfonyl chloride → (3aS,4S,6R,7aR)-4-(2-methoxyphenyl)-2-[(S)-2-(2-methoxyphenyl)propionyl]-6-tosyloxymethyl perhydroisoindol-4-ol

Beteiligte Stoffe

Reaktionsbedingungen

Reaktionsschritte

20.1 g of p-toluenesulphonyl chloride are added to a solution of 23.2 g of 6-hydroxymethyl-4-(2-methoxyphenyl)-2-[(S)-2-(2-methoxyphenyl)propionyl]perhydroisoindol-4-ol (mixture of the 2 diastereoisomers, 3aR,4R,6S,7aS,S and 3aS,4S,6R,7aR,S) and 14.9 cm3 of triethylamine in 300 cm3 of dichloromethane. After stirring at 20° C. for 48 hours, the reaction mixture is washed with 150 cm3 of water, then 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 0.06-0.20 mm, diameter 8.0 cm, height 45 cm), eluting under a pressure of 0.8 bar of nitrogen with a mixture of cyclohexane and ethyl acetate (50:50 by volume) and collecting fractions of 500 cm3. Fractions 14 to 17 are concentrated to dryness under reduced pressure. The residue obtained is subsequently chromatographed on a silica gel column (particle size 0.04-0.06 mm, diameter 7.5 cm, height 60 cm), eluting under a pressure of 0.8 bar of nitrogen with a mixture of cyclohexane and ethyl acetate (60:40 then 50:50 by volume) and collecting fractions of 500 cm3. Evaporation to dryness of fractions 22 to 26 gives 6.5 g of the (3aS,4S,6R,7aR)-4-(2-methoxyphenyl)-2-[(S)-2-(2-methoxyphenyl)propionyl]-6-tosyloxymethyl perhydroisoindol-4-ol diastereoisomer in the form of a thick white foam.

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