4-Fluorophenol → N-tert-butyloxycarbonyl4-(p-fluorophenoxymethyl)piperidine

HRID 413270Notes

Reaction equation

HRID 413270 reaction equation
N(C(OCC)=O)=NC(OCC)=O.[C:13]([O:17][C:18]([N:20]1[CH2:25][CH2:24][CH:23]([CH2:26][OH:27])[CH2:22][CH2:21]1)=[O:19])([CH3:16])([CH3:15])[CH3:14].[F:28][C:29]1[CH:34]=[CH:33][C:32](O)=[CH:31][CH:30]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>O1CCCC1>[C:13]([O:17][C:18]([N:20]1[CH2:25][CH2:24][CH:23]([CH2:26][O:27][C:32]2[CH:33]=[CH:34][C:29]([F:28])=[CH:30][CH:31]=2)[CH2:22][CH2:21]1)=[O:19])([CH3:16])([CH3:15])[CH3:14]

Participants

6

Reactant 4

HCID 97324-FluorophenolHCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 2764081Tert-butyl 4-(hydroxymethyl)piperidine-1-carboxylate

Product 1

HCID 15512457N-tert-butyloxycarbonyl4-(p-fluorophenoxymethyl)piperidine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Over the course of 30 minutes, 10.5 ml of diethyl azodicarboxylate are poured onto a mixture of 13.5 g of N-tert-butyloxycarbonyl-4-hydroxymethylpiperidine, 7.45 g of p-fluorophenol, 17.4 g of triphenylphosphine and 140 ml of tetrahydrofuran. After stirring for 12 hours at ambient temperature, the reaction mixture is concentrated, taken up in ether, washed with water and then 1N sodium hydroxide solution, and then washed with water. After drying, filtration and evaporation under reduced pressure, chromatography over silica gel (cyclohexane/ethyl acetate: 90/10) allows the expected product to be isolated.

Workup

  1. concentrationthe reaction mixture is concentrated
  2. washwashed with water
  3. wash1N sodium hydroxide solution, and then washed with water
  4. customAfter drying
  5. filtrationfiltration and evaporation under reduced pressure, chromatography over silica gel (cyclohexane/ethyl acetate: 90/10)
  6. customto be isolated

Sources & evidence

ORD record
ord-2cef51f8c8024ac0bcff6a9554704444
Source dataset
uspto-grants-2003_05
Patent number
US06566364B2

Reaction notes

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