Dicyclohexylcarbodiimide → (3aR,7aR)-7,7-diphenyl-2-[(S)-2-(2-methoxyphenyl)propionyl]-4-perhydroisoindolone

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Reaction Steps

1-Hydroxybenzotriazole (0.59 g) is added to a solution of (S)-2-[2-methoxyphenyl]propionic acid (0.75 g) of 84% optical purity prepared by the method of T. Matsumoto et al: Bull. Chem. Soc. Jpn., 58, 340 (1985), in dry dimethylformamide (15 cc) and the solution is then cooled to 0° C. N,N'-Dicyclohexylcarbodiimide (0.91 g) is added, the mixture is stirred for 1 hour at this temperature and a solution of (3aR,7aR)-7,7-diphenyl-4-perhydroisoindolone hydrochloride (1.44 g) and N,N-diisopropylethylamine (0.76 cc) in dimethylformamide (10 cc) is then added. The reaction mixture is stirred at 20° C. for 16 hours, diluted with ethyl acetate (100 cc) and concentrated to dryness under reduced pressure (2.7 kPa) after filtering off the precipitate. The residue is chromatographed on a silica gel column (0.2-0.063 mm, diameter 3 cm, height 40 cm), eluting under a nitrogen pressure of 0.7 bar with a mixture of cyclohexane and ethyl acetate (50/50 by volume) and collecting 125 cc fractions. Fractions 4 to 7 are combined and concentrated to dryness under reduced pressure (2.7 kPa). The residue is purified by dissolving in boiling isopropyl ether (60 cc) to which hexane (30 cc) had been added. The cooled solution is filtered and the filtrate is concentrated to dryness under reduced pressure (2.7 kPa) to give (3aR,7aR)-7,7-diphenyl-2-[(S)-2-(2-methoxyphenyl)propionyl]-4-perhydroisoindolone (1.2 g) in the form of a white meringue containing 10% of (3aR,7aR)-7,7-diphenyl-2-[(R)-2-(2-methoxyphenyl)propionyl]-4-perhydroisoindolone; [α]D20 =-181° (c=0.81, chloroform).

Provenance & Evidence