2-(trimethylsilyl)ethyl (1R,2S,5R)-2-((S)-3-benzyloxycarbonylamino-2-oxopyrrolidin-1-yl)-5-(hydroxyamino)cyclohexylcarbamate → 2-(trimethylsilyl)ethyl (1R,2S,5R)-2-((S)-3-benzyloxycarbonylamino-2-oxopyrrolidin-1-yl)-5-(tert-butylamino)cyclohexylcarbamate

HRID 1866106ノート

反応式

HRID 1866106 の反応式
[CH2:1]([O:8][C:9]([NH:11][C@H:12]1[CH2:16][CH2:15][N:14]([C@H:17]2[CH2:22][CH2:21][C@@H:20]([NH:23]O)[CH2:19][C@H:18]2[NH:25][C:26](=[O:34])[O:27][CH2:28][CH2:29][Si:30]([CH3:33])([CH3:32])[CH3:31])[C:13]1=[O:35])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C[Mg+].[Br-]>CC(C)=O>[CH2:1]([O:8][C:9]([NH:11][C@H:12]1[CH2:16][CH2:15][N:14]([C@H:17]2[CH2:22][CH2:21][C@@H:20]([NH:23][C:2]([CH3:7])([CH3:3])[CH3:1])[CH2:19][C@H:18]2[NH:25][C:26](=[O:34])[O:27][CH2:28][CH2:29][Si:30]([CH3:33])([CH3:32])[CH3:31])[C:13]1=[O:35])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

参加物

4

反応物 2

HCID 866181412-(trimethylsilyl)ethyl (1R,2S,5R)-2-((S)-3-benzyloxycarbonylamino-2-oxopyrrolidin-1-yl)-5-(hydroxyamino)cyclohexylcarbamateHCID 178418689HCID 178418689、化合物

生成物 1

HCID 866181402-(trimethylsilyl)ethyl (1R,2S,5R)-2-((S)-3-benzyloxycarbonylamino-2-oxopyrrolidin-1-yl)-5-(tert-butylamino)cyclohexylcarbamate収率 84.8%

試薬・触媒・溶媒 1

HCID 180Acetone溶媒

反応条件

温度
0 °C

実験手順

Example 1, Alternative Preparation, Step 5: A solution of 2-(trimethylsilyl)ethyl (1R,2S,5R)-2-((S)-3-benzyloxycarbonylamino-2-oxopyrrolidin-1-yl)-5-(hydroxyamino)cyclohexylcarbamate (350 mg, 0.69 mmol) in acetone (5 mL) was stirred at room temperature for 16 h. The mixture was concentrated in vacuo. The residue was dissolved in anhydrous THF (7 mL) and cooled to 0° C. A solution of MeMgBr (1.1 mL, 3M in diethyl ether, 5 eq) was added dropwise. The mixture was stirred at room temperature for 1.5 h. The reaction was quenched with water (5 mL) at 0° C. The mixture was diluted with ethyl acetate (100 mL) and filtered through a pad of celite. The filtrate was washed with brine (30 mL). The solution was dried over anhydrous MgSO4, filtered, and concentrated in vacuo. The residue was dissolved in 2 ml of acetonitrile and 1 ml of CS2 was added. The mixture was stirred at room temperature for 1 hours. The solvent was removed and the crude product was purified by silica gel column chromatography, using 1.5% of methanol in dichloromethane as the eluant, to provide the desired 2-(trimethylsilyl)ethyl (1R,2S,5R)-2-((S)-3-benzyloxycarbonylamino-2-oxopyrrolidin-1-yl)-5-(tert-butylamino)cyclohexylcarbamate (160 mg, 42%). LC/MS found [M+H]−=547.

後処理

  1. customExample 1, Alternative Preparation, Step 5
  2. concentrationThe mixture was concentrated in vacuo
  3. dissolutionThe residue was dissolved in anhydrous THF (7 mL)
  4. customThe reaction was quenched with water (5 mL) at 0° C
  5. additionThe mixture was diluted with ethyl acetate (100 mL)
  6. filtrationfiltered through a pad of celite
  7. washThe filtrate was washed with brine (30 mL)
  8. dry with materialThe solution was dried over anhydrous MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. dissolutionThe residue was dissolved in 2 ml of acetonitrile
  12. addition1 ml of CS2 was added
  13. stirringThe mixture was stirred at room temperature for 1 hours
  14. customThe solvent was removed
  15. customthe crude product was purified by silica gel column chromatography

出典と根拠

ORDレコード
ord-eb9d4a29fef94cb7922dbe1675736a5f
出典データセット
uspto-grants-2009_12
特許番号
US07629351B2

反応ノート

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