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

HRID 132751

反応式

HRID 132751 の反応式
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([OH:26])[CH2:9][CH2:10][CH2:11][C:12]([N:14]2[CH:18]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[CH2:17][O:16][C:15]2=[O:25])=[O:13])=[CH:4][CH:3]=1.[F:27][C:28]1[CH:33]=[CH:32][C:31]([N:34]=[CH:35][C:36]2[CH:43]=[CH:42][C:39]([C:40]#[N:41])=[CH:38][CH:37]=2)=[CH:30][CH:29]=1.C(N(C(C)C)CC)(C)C.C[Si](Cl)(C)C.C(O)(=O)C(C(C(O)=O)O)O.C(=O)(O)[O-].[Na+]>ClCCl.[Ti](Cl)(Cl)(Cl)Cl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([OH:26])[CH2:9][CH2:10][CH:11]([C:12]([N:14]2[CH:18]([C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH2:17][O:16][C:15]2=[O:25])=[O:13])[CH:35]([C:36]2[CH:43]=[CH:42][C:39]([C:40]#[N:41])=[CH:38][CH:37]=2)[NH:34][C:31]2[CH:30]=[CH:29][C:28]([F:27])=[CH:33][CH:32]=2)=[CH:4][CH:3]=1

参加物

9

反応物 6

HCID 8752,3-Dihydroxybutanedioic AcidHCID 6397ChlorotrimethylsilaneHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 9135414-[(4-Fluoro-phenylimino)methyl]benzonitrileHCID 121116173-[5-(4-Fluorophenyl)-5-hydroxy-1-oxopentyl]-4-phenyl-2-oxazolidinone

生成物 1

HCID 222520644-[5-(4-Fluorophenyl)-1-(4-fluorophenylamino)-5-hydroxy-2-(2-oxo-4-phenyloxazolidine-3-carbonyl)-pentyl]-benzonitrile

試薬・触媒・溶媒 2

HCID 24193Titanium Tetrachloride触媒HCID 6344Dichloromethane溶媒

反応条件

温度
-10 °C

実験手順

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 and 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 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).

後処理

  1. customdid not exceed −5° C
  2. temperaturecooled to −25° C
  3. stirringThe dark mixture was stirred at a temperature
  4. stirringstirred at room temperature for another hour
  5. stirringthe mixture was again stirred for 1 hour
  6. concentrationFollowing magnesium sulfate and concentrated to about 10 ml
  7. additionthe addition of 2 ml of bistrimethylsilylacetamide
  8. temperaturethe mixture was heated
  9. temperatureat reflux for 30 min
  10. concentrationconcentrated under reduced pressure
  11. customThe residue was crystallized
  12. filtrationThe product was filtered off with suction
  13. customdried under reduced pressure
  14. customThis gave the product of molecular weight 653.81 (C37H37F2N3O4Si)

出典と根拠

ORDレコード
ord-b851b60b1cca41e7b1edabd6a281b28a
出典データセット
uspto-grants-2008_06
特許番号
US07388004B2

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