Potassium Carbonate → (3aRS,7aRS)-7,7-bis(3-fluorophenyl)-2-[1-imino-2-(2-methoxyphenyl)ethyl]perhydro-4-isoindolone

温度

25 °C

A suspension of (2-methoxyphenyl)acetamide (0.9 g) in dry dichloromethane (3 cc) is treated with triethyloxonium tetrafluoborate (1.14 g) and the solution obtained is stirred for 20 hours at 25° C. After cooling to 0° C., a solution of 7,7-bis-(3-fluorophenyl)-4-perhydroisoindolone hydrochloride (1.5 g) and triethylamine (1.4 cc) in dichloromethane (9 cc) is added to the reaction mixture. The reaction mixture is stirred for 30 minutes at 25° C., then refluxed 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 and filtering and concentrating the filtrate to dryness under reduced pressure (2.7 kPa), the residue is chromatographed on an alumina column (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]-4-perhydroisoindolone (0.54 g) in the form of a pale yellow meringue.

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

ORDレコード

ord-8bd06d3b1e0b481090af312c4a603166

出典データセット

uspto-grants-1992_04

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US05102667