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. and 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)-4-perhydroisoindolone 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 and filtered and the filtrate is concentrated to dryness under reduced pressure (2.7 kPa). The residue is chromatographed on a silica gel column (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) 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 from acetonitrile. The crystals are drained, washed with isopropyl ether and dried. (3aRS,7aRS)-7,7-bis-(3-fluorophenyl)-2-(phenylacetyl)-4-perhydroisoindolone (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. concentrationthe filtrate is concentrated to dryness under reduced pressure (2.7 kPa)
6. customThe residue is chromatographed on a silica gel column (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)
9. customcollecting 15 cc fractions
10. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
11. customthe product obtained
12. customis recrystallized from acetonitrile
13. washwashed with isopropyl ether
14. customdried