反应详情

Trifluoroacetic acid (3 drops) is added to a solution of 4,4-bis-(2-fluorophenyl)-cyclohexenone (4.3 g) and N-butoxymethyl-N-trimethylsilylmethylbenzylamine (5.8 cc) in dry dichloromethane (30 cc). The reaction mixture is brought to reflux and then stirred for 16 hours after having allowed the temperature to return to 25° C. N-Butoxymethyl-N-trimethylsilymethylbenzylamine (2.5 cc) and trifluoroacetic acid (3 drops) are added and the mixture is stirred for 3 hours under reflux. The reaction mixture is treated with potassium carbonate (3 g) and stirred for 15 minutes. After filtering and concentrating the filtrate 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 4 cm, height 32 cm), eluting under a nitrogen pressure of 0.5 bar with a mixture of cyclohexane and ethyl acetate (85/15) and collecting 20 cc fractions. Fractions 13 to 22 are combined and concentrated to dryness under reduced pressure (2.7 kPa) to give (3aRS,7aRS)-2-benzyl-7,7-bis-(2-fluorophenyl)-4-perhydroisoindolone (2.28 g). m.p.=138° C.

1. temperatureto reflux
2. customto return to 25° C
3. stirringthe mixture is stirred for 3 hours
4. temperatureunder reflux
5. stirringstirred for 15 minutes
6. filtrationAfter filtering
7. concentrationconcentrating the filtrate to dryness under reduced pressure (2.7 kPa)
8. customthe residue is chromatographed on a silica gel column (particle size 0.04-0.063 mm, diameter 4 cm, height 32 cm)
9. washeluting under a nitrogen pressure of 0.5 bar
10. additionwith a mixture of cyclohexane and ethyl acetate (85/15)
11. customcollecting 20 cc fractions
12. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)