反应详情

N,N'-Carbonyldiimidazole (1 g) is added to a solution of 2-methoxyphenylacetic acid (1 g) in dry dichloromethane (30 cc), cooled to +5° C. The mixture is stirred for 40 minutes at +5° C. and a solution of (3aRS,7aRS)-7,7-diphenyl-4-perhydroisoindolone hydrochloride (2 g) and triethylamine (1.7 cc) in dichloromethane (40 cc) is then added. The reaction mixture is stirred at 20° C. for 16 hours, then washed with 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 1.8 cm, height 13 cm), eluting with ethyl acetate and collecting 25 cc fractions. Fractions 3 to 5 are combined and concentrated to dryness under reduced pressure (2.7 kPa). The residue is crystallized from a mixture of acetonitrile (5 cc) and isopropyl ether (10 cc). The crystals are drained, washed with isopropyl ether (25 cc) and dried. (3aR,7aR)-(-)-7,7-diphenyl-2-[(2-methoxyphenyl)acetyl]-4-perhydroisoindolone (1.7 g) is obtained in the form of white crystals melting at 200° C.; [α]20D =-274° (c=0.49, acetic acid).

1. temperaturecooled to +5° C
2. stirringThe reaction mixture is stirred at 20° C. for 16 hours
3. washwashed with 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 1.8 cm, height 13 cm)
8. washeluting with ethyl acetate
9. customcollecting 25 cc fractions
10. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
11. customThe residue is crystallized from a mixture of acetonitrile (5 cc) and isopropyl ether (10 cc)
12. washwashed with isopropyl ether (25 cc)
13. customdried