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

HRID 609686Notes

Reaction equation

HRID 609686 reaction equation
[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]

Participants

5

Reactant 3

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-eb9f8a59b9a0471693d5485b5457d74d
Source dataset
uspto-grants-1999_12
Patent number
US05998412

Reaction notes

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