Sodium hydride → tert-Butyl 4-[4-(trifluoromethoxy)phenoxy]piperidine-1-carboxylate

HRID 1043526Notes

Reaction equation

HRID 1043526 reaction equation
[C:1]([N:8]1[CH2:13][CH2:12][CH:11]([OH:14])[CH2:10][CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[H-].[Na+].[F:17][C:18]([F:29])([F:28])[O:19][C:20]1[CH:27]=[CH:26][C:23](CBr)=[CH:22][CH:21]=1>CN(C=O)C>[C:4]([O:3][C:1]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:23]2[CH:22]=[CH:21][C:20]([O:19][C:18]([F:17])([F:28])[F:29])=[CH:27][CH:26]=2)[CH2:10][CH2:9]1)=[O:2])([CH3:7])([CH3:6])[CH3:5]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 1427851-(Bromomethyl)-4-(trifluoromethoxy)benzeneHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylate

Product 1

HCID 23081100tert-Butyl 4-[4-(trifluoromethoxy)phenoxy]piperidine-1-carboxylateYield 802.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

N-Boc-4-hydroxy piperidine (2.01 g, 1.0 mmol) was dissolved in DMF (30 mL), added sodium hydride (60%, 0.6 g, 15 mmol) in ice-bath, stirred for 30 min, added p-trifluoromethoxy benzyl bromide (3.06 g, 12 mmol), after which resumed to stir for 15 h at room temperature, added ice water (30 mL) in ice-bath to quench reaction. Extracted by dichloromethane (30 mL*2), combined organic phases, the organic phases were washed by water and saturated saline respectively, dried by anhydrous sodium sulfate, concentrated column chromatography (petroleum ether: ethyl acetate=10:1) to give 2.9 g light yellow liquid, yield was 78%.

Workup

  1. stirringto stir for 15 h at room temperature
  2. customto quench
  3. customreaction
  4. extractionExtracted by dichloromethane (30 mL*2)
  5. washthe organic phases were washed by water and saturated saline respectively
  6. dry with materialdried by anhydrous sodium sulfate
  7. concentrationconcentrated column chromatography (petroleum ether: ethyl acetate=10:1)

Sources & evidence

ORD record
ord-0992ad7e403648bdb79b36c49af19840
Source dataset
uspto-grants-2013_10
Patent number
US08563547B2

Reaction notes

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