反应详情

温度

0 °C

A solution of (2-methoxyphenyl)acetic acid (0.46 g) in dry dichloromethane (15 cc) is cooled to 0° C., then treated with N,N'-carbonyldiimidazole (0.45 g) and stirred for 1 hour at 0° C. A solution of 7,7-bis(3-fluorophenyl)perhydro-4-isoindolone hydrochloride (1 g) and triethylamine (0.76 cc) in dichloromethane (20 cc) is added dropwise. The reaction mixture is stirred for 3 hours at 25° C. and then washed with water (2×50 cc) and with saturated sodium chloride solution (50 cc). The organic phase is 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 (particle size 0.04-0.063 mm, diameter 2.2 cm, height 23 cm), eluting under a nitrogen pressure of 0.5 bar with a mixture of cyclohexane and ethyl acetate (70:30 by volume) and collecting 15-cc fractions. Fractions 4 to 9 are combined and concentrated to dryness under reduced pressure (2.7 kPa), and the product obtained is recrystallized in acetonitrile. The crystals are drained, washed with isopropyl ether and dried. (3aRS,7aRS)-7,7-Bis(3-fluorophenyl)-2-(phenylacetyl)perhydro-4-isoindolone (0.76 g) is obtained. M.p. 194° C.

1. stirringThe reaction mixture is stirred for 3 hours at 25° C.
2. washwashed with water (2×50 cc) and with saturated sodium chloride solution (50 cc)
3. dry with materialThe organic phase is dried 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 (particle size 0.04-0.063 mm, diameter 2.2 cm, height 23 cm)
7. washeluting under a nitrogen pressure of 0.5 bar
8. additionwith a mixture of cyclohexane and ethyl acetate (70:30 by volume)
9. customcollecting 15-cc fractions
10. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
11. customthe product obtained
12. customis recrystallized in acetonitrile
13. washwashed with isopropyl ether
14. customdried