反应详情

N,N'-Carbonyldiimidazole (2.43 g) is added to a solution of 2-dimethylaminophenylacetic acid (2.68 g) in dry dichloromethane (50 cc), cooled to +5° C. The mixture is stirred at +5° C. for 90 minutes and a solution of (3aR,7aR)-7,7-diphenyl-4-perhydroisoindolone hydrochloride (4.9 g) and triethylamine (4.2 cc) in dichloromethane (50 cc) is then added. The reaction mixture is stirred at 20° C. for 16 hours, then washed with water (2×100 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 5 cm, height 50 cm), eluting under a nitrogen pressure of 0.7 bar with a mixture of cyclohexane and ethyl acetate (40/60 by volume) and collecting 125 cc fractions. Fractions 5 to 20 are combined and concentrated to dryness under reduced pressure (2.7 kPa). The residue is crystallized from a mixture of acetonitrile (40 cc) and isopropyl ether (200 cc). The crystals are drained, washed with isopropyl ether and dried. (3aR,7aR)-7,7-diphenyl-2-[2-(2-dimethylaminophenyl)acetyl]-4-perhydroisoindolone (2.58 g) is obtained in the form of white crystals, melting at 190° C.; [α]D20 =-242° (c=1.18, chloroform)

1. temperaturecooled to +5° C
2. stirringThe reaction mixture is stirred at 20° C. for 16 hours
3. washwashed with water (2×100 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 5 cm, height 50 cm)
8. washeluting under a nitrogen pressure of 0.7 bar
9. additionwith a mixture of cyclohexane and ethyl acetate (40/60 by volume)
10. customcollecting 125 cc fractions
11. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
12. customThe residue is crystallized from a mixture of acetonitrile (40 cc) and isopropyl ether (200 cc)
13. washwashed with isopropyl ether
14. customdried