Chlorotrimethylsilane → 11beta-Fluoro-7alpha-methylestr-4-ene-3,17-dione

HRID 2215945ノート

反応式

HRID 2215945 の反応式
[Br-].[Li+].C[Mg]Br.[F:6][C@H:7]1[CH2:24][C@@:22]2([CH3:23])[C@@H:18]([CH2:19][CH2:20][C:21]2=[O:25])[C@H:17]2[C@H:8]1[C@@H:9]1[C:14]([CH:15]=[CH:16]2)=[CH:13][C:12](=[O:26])[CH2:11][CH2:10]1.[CH3:27][Si](Cl)(C)C>O1CCCC1.C(OCC)C.ClCCl.[Cu](I)I.CN1C(=O)N(C)CCC1>[F:6][C@H:7]1[CH2:24][C@@:22]2([CH3:23])[C@@H:18]([CH2:19][CH2:20][C:21]2=[O:25])[C@H:17]2[C@H:8]1[C@@H:9]1[C:14]([CH2:15][C@H:16]2[CH3:27])=[CH:13][C:12](=[O:26])[CH2:11][CH2:10]1

参加物

10

反応物 4

HCID 6397ChlorotrimethylsilaneHCID 82050Lithium BromideHCID 1117374411beta-Fluoroestra-4,6-diene-3,17-dioneHCID 178418573HCID 178418573、化合物

生成物 1

HCID 1019314411beta-Fluoro-7alpha-methylestr-4-ene-3,17-dione

試薬・触媒・溶媒 5

HCID 83717Copper iodide触媒HCID 3283Diethyl Ether溶媒HCID 6344Dichloromethane溶媒HCID 8028Tetrahydrofuran溶媒HCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-溶媒2 回

反応条件

温度
0 °C

実験手順

A suspension of 15.2 g (79.8 mmol) of copper iodide in 70 ml of dry tetrahydrofuran is cooled to 0° C., mixed with 28.7 g (330 mmol) of lithium bromide and 27.8 ml of DMPU, stirred first for 30 minutes at this temperature and then cooled to −30° C. While being stirred, 52 ml of methylmagnesium bromide in diethyl ether (3 molar solution) is then added in drops, stirred for another 30 minutes, and the gray-colored suspension is mixed with a solution that consists of 10.0 g (34.7 mmol) of 11β-fluoroestra-4,6-diene-3,17-dione, 24.3 ml of DMPU and 23 ml of trimethylsilyl chloride in 60 ml of dichloromethane. After the addition is completed, it is allowed to stir for another 1.5 hours between −30→−10° C., the cold bath is removed, and 35 ml of ethyl acetate is carefully added at room temperature while being stirred vigorously. For working-up, the reaction solution is diluted with ethyl acetate, washed with saturated aqueous ammonium chloride solution that is free of copper, and the organic phase is dried on sodium sulfate. The crude product is chromatographed on silica gel (hexane-ethyl acetate, gradient of up to 1:1), yield 3.1 g (30%).

後処理

  1. temperaturecooled to −30° C
  2. stirringWhile being stirred
  3. stirringstirred for another 30 minutes
  4. additionthe gray-colored suspension is mixed with a solution that
  5. additionAfter the addition
  6. stirringto stir for another 1.5 hours between −30→−10° C.
  7. customthe cold bath is removed
  8. addition35 ml of ethyl acetate is carefully added at room temperature
  9. stirringwhile being stirred vigorously
  10. additionthe reaction solution is diluted with ethyl acetate
  11. washwashed with saturated aqueous ammonium chloride solution that
  12. customthe organic phase is dried on sodium sulfate
  13. customThe crude product is chromatographed on silica gel (hexane-ethyl acetate, gradient of up to 1:1), yield 3.1 g (30%)

出典と根拠

ORDレコード
ord-b8a29fabdeb44b1fa400f371fbefaa0f
出典データセット
uspto-grants-2006_09
特許番号
US07109360B1

反応ノート

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