Sodium hydride → N-tert-butoxycarbonyl-4-[5-fluoro-1-(2-trimethylsilylethanesulfonyl)indol-3-yl]piperidine

HRID 609686ノート

反応式

HRID 609686 の反応式
[H-].[Na+].[C:3]([O:7][C:8]([N:10]1[CH2:15][CH2:14][CH:13]([C:16]2[C:24]3[C:19](=[CH:20][CH:21]=[C:22]([F:25])[CH:23]=3)[NH:18][CH:17]=2)[CH2:12][CH2:11]1)=[O:9])([CH3:6])([CH3:5])[CH3:4].[CH3:26][Si:27]([CH3:35])([CH3:34])[CH2:28][CH2:29][S:30](Cl)(=[O:32])=[O:31]>CN(C=O)C>[C:3]([O:7][C:8]([N:10]1[CH2:11][CH2:12][CH:13]([C:16]2[C:24]3[C:19](=[CH:20][CH:21]=[C:22]([F:25])[CH:23]=3)[N:18]([S:30]([CH2:29][CH2:28][Si:27]([CH3:35])([CH3:34])[CH3:26])(=[O:32])=[O:31])[CH:17]=2)[CH2:14][CH2:15]1)=[O:9])([CH3:6])([CH3:4])[CH3:5]

参加物

5

反応物 3

HCID 24758Sodium hydrideHCID 98370862-(Trimethylsilyl)ethane-1-sulfonyl chlorideHCID 227144175-fluoro-3-(1-tert-butoxycarbonylpiperidin-4-yl)-1H-indole

生成物 1

HCID 22615698N-tert-butoxycarbonyl-4-[5-fluoro-1-(2-trimethylsilylethanesulfonyl)indol-3-yl]piperidine収率 84%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

Sodium hydride (96 mg, 4.07 mmol) was added to a solution of N-tert-butoxycarbonyl-4-(5-fluoroindol-3-yl)piperidine (1.28 g, 4.07 mmol), [prepared as described in Step 1, above] in DMF (6 ml) at 0° C. and the reaction mixture was stirred for 30 min. 2-Trimethylsilylethanesulfonyl chloride (820 mg, 4.07 mmol) was added and the reaction mixture was slowly warmed to RT over 30 min. After 2.5 h, the reaction mixture was quenched with water (10 ml) and the product was extracted into methylene chloride. The combined organic layers were dried over MgSO4 and concentrated in vacuo. Due to incomplete reaction the above steps were repeated on the isolated crude reaction mixture. The final residue was chromatographed (PTLC, SiO2, 20% ethyl acetate/hexanes) to afford N-tert-butoxycarbonyl-4-[5-fluoro-1-(2-trimethylsilylethanesulfonyl)indol-3-yl]piperidine (84%) as a clear oil.

後処理

  1. waitAfter 2.5 h
  2. customthe reaction mixture was quenched with water (10 ml)
  3. extractionthe product was extracted into methylene chloride
  4. dry with materialThe combined organic layers were dried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customDue to incomplete reaction the above steps
  7. customisolated crude
  8. customreaction mixture
  9. customThe final residue was chromatographed (PTLC, SiO2, 20% ethyl acetate/hexanes)

出典と根拠

ORDレコード
ord-eb9f8a59b9a0471693d5485b5457d74d
出典データセット
uspto-grants-1999_12
特許番号
US05998412

反応ノート

読み込み中…