反应详情

N,N'-carbonyldiimidazole (1 g) is added to a solution, cooled to +5° C., of 2-dimethylaminophenylacetic acid (1.1 g) in dry dichloromethane (30 cc). The mixture is stirred for 30 minutes at +5° C. and a solution of (3aRS, 7aRS)- 7,7-diphenylperhydro-4-isoindolone hydrochloride (2.03 g) and triethylamine (1.68 cc) in dichloromethane (20 cc) is then added. The reaction mixture is stirred at 20° C. for 24 hours, then washed with water (3×200 cc), dried over magnesium sulphate, filtered and concentrated to dryness under reduced pressure (2.7 kPa). The residue is chromatographed on a column of silica gel (0.2-0.063 mm, diameter 3 cm, height 25 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 8 to 26 are combined and concentrated to dryness under reduced pressure (2.7 kPa). The residue is crystallized in isopropyl ether (40 cc). The crystals are drained, washed with isopropyl ether and dried. (3aRS, 7aRS)-7,7-Diphenyl-2-[2(2-dimethylaminophenyl)acetyl]perhydro-4-isoindolone (0.9 g) is obtained in the form of white crystals, m.p. 150° C.

1. stirringThe reaction mixture is stirred at 20° C. for 24 hours
2. washwashed with water (3×200 cc)
3. dry with materialdried over magnesium sulphate
4. filtrationfiltered
5. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
6. customThe residue is chromatographed on a column of silica gel (0.2-0.063 mm, diameter 3 cm, height 25 cm)
7. washeluting under a nitrogen pressure of 0.7 bar
8. additionwith a mixture of cyclohexane and ethyl acetate (40:60 by volume)
9. customcollecting 125-cc fractions
10. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
11. customThe residue is crystallized in isopropyl ether (40 cc)
12. washwashed with isopropyl ether
13. customdried