反应详情

N,N'-Carbonyldiimidazole (0.49 g) is added to a solution of (S)-2-phenylbutyric acid (0.5 g) in dry dichloromethane (15 cc), cooled to +5° C. The mixture is stirred for 30 minutes at +5° C. and a solution of (3aR,7aR)-7,7-diphenyl-4-perhydroisoindolone hydrochloride (0.98 g) and triethylamine (0.42 cc) in dichloromethane (20 cc) is then added. The reaction mixture is stirred at 20° C. for 16 hours, then washed with distilled water (2×50 cc), dried over magnesium sulphate and filtered and the filtrate is concentrated to dryness under reduced pressure (2.7 kPa). The residue is chromatographed on a silica gel column (0.2-0.063 mm, diameter 1.6 cm, height 9.7 cm), eluting with a mixture of ethyl acetate and cyclohexane (80/20 by volume) and collecting 30 cc fractions. The first fraction is concentrated to dryness under reduced pressure (2.7 kPa). The residue is re-chromatographed on a silica gel column (0.2-0.063 mm, diameter 1.3 cm, height 14.5 cm), eluting with a mixture of cyclohexane and ethyl acetate (70/30 by volume) and collecting 50 cc fractions. Fractions 1 to 3 are combined and concentrated to dryness under reduced pressure (2.7 kPa). (3aR,7aR)-7,7-diphenyl-2-[(S)-2-phenylbutyryl]-4-perhydroisoindolone (0.54 g) is obtained in the form of a white meringue. [α]D20 =-216° (c=1, methanol).

1. temperaturecooled to +5° C
2. stirringThe reaction mixture is stirred at 20° C. for 16 hours
3. washwashed with distilled water (2×50 cc)
4. dry with materialdried over magnesium sulphate
5. filtrationfiltered
6. concentrationthe filtrate is concentrated to dryness under reduced pressure (2.7 kPa)
7. customThe residue is chromatographed on a silica gel column (0.2-0.063 mm, diameter 1.6 cm, height 9.7 cm)
8. washeluting with a mixture of ethyl acetate and cyclohexane (80/20 by volume)
9. customcollecting 30 cc fractions
10. concentrationThe first fraction is concentrated to dryness under reduced pressure (2.7 kPa)
11. customThe residue is re-chromatographed on a silica gel column (0.2-0.063 mm, diameter 1.3 cm, height 14.5 cm)
12. washeluting with a mixture of cyclohexane and ethyl acetate (70/30 by volume)
13. customcollecting 50 cc fractions
14. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)