反应详情

1H hydroxybenzotriazole (0.59 g) is added to a solution of 84% optically pure (S)-2-(2-methoxyphenyl)propionic acid (0.75 g), prepared according to 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 then added, the mixture is stirred for 1 hour at this temperature and a solution of (3aR, 7aR)-7,7-diphenylperhydro-4-isoindolone 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 the precipitate has been filtered off. The residue is chromatographed on a column of silica gel (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 dissolution in boiling isopropyl ether (60 cc) to which hexane (30 cc) is added. The cooled solution is filtered and the filtrate concentrated to dryness under reduced pressure (2.7 kPa) to give (3aR, 7aR)-7,7-diphenyl-2-[(S)-2-(2-methoxyphenyl)propionyl]perhydro-4-isoindolone (1.2 g) in the form of a white meringue-like product containing (3aR, 7aR)-7,7-diphenyl-2-[(R)-2-(2-methoxyphenyl)propionyl]perhydro-4-isoindolone (10%); [α]D20 =-181° (c=0.81, chloroform).

1. customprepared
2. stirringThe reaction mixture is stirred at 20° C. for 16 hours
3. concentrationconcentrated to dryness under reduced pressure (2.7 kPa) after the precipitate
4. filtrationhas been filtered off
5. customThe residue is chromatographed on a column of silica gel (0.2-0.063 mm, diameter 3 cm, height 40 cm)
6. washeluting under a nitrogen pressure of 0.7 bar
7. additionwith a mixture of cyclohexane and ethyl acetate (50:50 by volume)
8. customcollecting 125-cc fractions
9. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
10. customThe residue is purified by dissolution
11. additionis added
12. filtrationThe cooled solution is filtered
13. concentrationthe filtrate concentrated to dryness under reduced pressure (2.7 kPa)