2,3-Dihydroxybutanedioic Acid → 4-[5-(4-Fluorophenyl)-1-(4-fluorophenylamino)-5-hydroxy-2-(2-oxo-4-phenyloxazolidine-3-carbonyl)-pentyl]-benzonitrile

温度

-10 °C

Under argon, 2.5 g of 3-[5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyloxazolidin-2-one were dissolved in 30 ml of dichloromethane. 3.9 g of 4-[(4-fluorophenylimino)-methyl]-benzonitrile were added and the mixture was cooled to −10° C. 6.4 ml of diisopropylethylamine and, over a period of 30 min, 4.05 ml of trimethylsilyl chloride were added to this mixture so that the temperature did not exceed −5° C. The mixture was stirred at this temperature for 1 additional hour and then cooled to −25° C. 0.8 ml of titanium tetrachloride were then added slowly. The dark mixture was stirred at a temperature ranging from −25 to −30° C. overnight and then decomposed using 35 ml of a 7 percent strength solution of tartaric acid. The solution was then stirred at room temperature for another hour. 15 ml of a 20 percent strength solution of sodium bicarbonate were then added, and the mixture was again stirred for 1 hour. Following phase separation, the organic phase was washed with 30 ml of water, dried over magnesium sulfate and concentrated to about 10 ml. Following the addition of 2 ml of bistrimethylsilylacetamide, the mixture was heated at reflux for 30 min and then concentrated under reduced pressure. The residue was crystallized using ethyl acetate/heptane. The product was filtered off with suction and dried under reduced pressure. This gave the product of molecular weight 653.81 (C37H37F2N3O4Si); MS (ESI+): 654.3 (M+H+), 582.2 (M+H+−Si(CH3)3).

1. customdid not exceed −5° C
2. temperaturecooled to −25° C
3. stirringThe dark mixture was stirred at a temperature
4. stirringThe solution was then stirred at room temperature for another hour
5. stirringthe mixture was again stirred for 1 hour
6. customFollowing phase separation
7. washthe organic phase was washed with 30 ml of water
8. dry with materialdried over magnesium sulfate
9. concentrationconcentrated to about 10 ml
10. additionthe addition of 2 ml of bistrimethylsilylacetamide
11. temperaturethe mixture was heated
12. temperatureat reflux for 30 min
13. concentrationconcentrated under reduced pressure
14. customThe residue was crystallized
15. filtrationThe product was filtered off with suction
16. customdried under reduced pressure
17. customThis gave the product of molecular weight 653.81 (C37H37F2N3O4Si)

ORDレコード

ord-03b08d31f4ad458697a4e25ef2c988c6

出典データセット

uspto-grants-2009_08

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07579339B2