Sodium hydride → Tert-butyl 4-(4-nitro-2-(trifluoromethyl)phenoxy)piperidine-1-carboxylate

HRID 1700278Notes

Reaction equation

HRID 1700278 reaction equation
[OH:1][CH:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1.[H-].[Na+].F[C:18]1[CH:23]=[CH:22][C:21]([N+:24]([O-:26])=[O:25])=[CH:20][C:19]=1[C:27]([F:30])([F:29])[F:28]>CN(C=O)C.O>[C:11]([O:10][C:8]([N:5]1[CH2:4][CH2:3][CH:2]([O:1][C:18]2[CH:23]=[CH:22][C:21]([N+:24]([O-:26])=[O:25])=[CH:20][C:19]=2[C:27]([F:28])([F:29])[F:30])[CH2:7][CH2:6]1)=[O:9])([CH3:14])([CH3:13])[CH3:12]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 949542-Fluoro-5-nitrobenzotrifluorideHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylate

Product 1

HCID 22181018Tert-butyl 4-(4-nitro-2-(trifluoromethyl)phenoxy)piperidine-1-carboxylateYield 80%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To 4-hydroxy-N-(t-butoxycarbonyl)piperidine (10.0 g) in DMF was added NaH (2.2 g) at ambient temperature. The reaction mixture was stirred at ambient temperature for 2 hours. 4-Flouro-3-trifluoromethyl-1-nitrobenzene (5.3 mL) was added and the reaction mixture was stirred overnight at ambient temperature. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with aqueous NaHCO3 and aqueous HCl, dried over sodium sulfate, concentrated and purified on silica gel column (hexane/ethyl acetate, gradient) to afford a compound of formula (C), 4-(N-(t-butoxycarbonyl)piperidin-4-yl)oxy-3-trifluoromethyl-1-nitrobenzene in 80% yield.

Workup

  1. stirringthe reaction mixture was stirred overnight at ambient temperature
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed with aqueous NaHCO3 and aqueous HCl
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated
  6. custompurified on silica gel column (hexane/ethyl acetate, gradient)

Sources & evidence

ORD record
ord-efc56e191a3540378b69e4aa66e8f17e
Source dataset
uspto-grants-2002_02
Patent number
US06350761B1

Reaction notes

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