反应详情

N,N'-Carbonyldiimidazole (1.14 g) is added to a solution of 2-hydroxyphenylacetic acid (1.06 g) in dry dichloromethane (30 cc), cooled to +5° C. The mixture is stirred for 30 minutes at +5° C. and a solution of (3aRS,7aRS)-7,7-diphenyl-4-perhydroisoindolone hydrochloride (2.23 g) and triethylamine (1.96 cc) in dichloromethane (20 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 4 cm, height 40 cm), eluting under a nitrogen pressure of 0.7 bar with a mixture of cyclohexane and ethyl acetate (70/30 by volume) and collecting 125 cc fractions. Fractions 4 to 11 are combined and concentrated to dryness under reduced pressure (2.7 kPa). The residue is crystallized from a mixture of acetonitrile (15 cc) and isopropyl ether (30 cc). The crystals are drained, washed with isopropyl ether and dried. (3aRS,7aRS)-7,7-diphenyl-2-[(2-hydroxyphenyl)acetyl]-4-perhydroisoindolone (0.8 g) is obtained in the form of white crystals melting at 232° C.

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 4 cm, height 40 cm)
8. washeluting under a nitrogen pressure of 0.7 bar
9. additionwith a mixture of cyclohexane and ethyl acetate (70/30 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 (15 cc) and isopropyl ether (30 cc)
13. washwashed with isopropyl ether
14. customdried