反应详情

温度

25 °C

A suspension of (2-methoxyphenyl)acetamide (0.9 g) in dry dichloromethane (3 cc) is treated with triethyloxonium tetrafluoroborate (1.14 g), and the solution obtained stirred for 20 hours at 25° C. After cooling to 0° C., a solution of 7,7-bis(3-fluorophenyl)perhydro-4-isoindolone hydrochloride (1.5 g) and triethylamine (1.4 cc) in dichloromethane (9 cc) is added to the reaction medium. The reaction mixture is stirred for 30 minutes at 25° C., then heated to reflux for 5 hours and finally stirred for a further 16 hours at 25° C. Saturated potassium carbonate solution (50 cc) is added, the mixture is stirred and filtered and the organic phase is washed with water (2×50 cc). After drying over magnesium sulphate, filtration and concentration to dryness under reduced pressure (2.7 kPa), the residue is chromatographed on a column of alumina (diameter 2.6 cm, height 24 cm), eluting under a nitrogen pressure of 0.5 bar with a mixture of 1,2 -dichloroethane and methanol (95:5 by volume) and collecting 15-cc fractions. Fractions 7 to 25 are combined and concentrated to dryness under reduced pressure (2.7 kPa) to give (3aRS,7aRS)-7,7-bis(3-fluorophenyl)-2-[1-imino-2-(2-methoxyphenyl)ethyl]perhydro-4-isoindolone (0.54 g) in the form of a pale yellow meringue-like product.

1. customthe solution obtained
2. temperatureAfter cooling to 0° C.
3. stirringThe reaction mixture is stirred for 30 minutes at 25° C.
4. temperatureheated
5. temperatureto reflux for 5 hours
6. stirringfinally stirred for a further 16 hours at 25° C
7. stirringthe mixture is stirred
8. filtrationfiltered
9. washthe organic phase is washed with water (2×50 cc)
10. dry with materialAfter drying over magnesium sulphate, filtration and concentration to dryness under reduced pressure (2.7 kPa)
11. customthe residue is chromatographed on a column of alumina (diameter 2.6 cm, height 24 cm)
12. washeluting under a nitrogen pressure of 0.5 bar
13. additionwith a mixture of 1,2 -dichloroethane and methanol (95:5 by volume)
14. customcollecting 15-cc fractions
15. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)