4-Fluorophenol → 1-Benzyl-4-(2-(4-fluorophenoxy)ethyl)piperidine

HRID 380492Notes

Reaction equation

HRID 380492 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][CH2:15][OH:16])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:17][C:18]1[CH:23]=[CH:22][C:21](O)=[CH:20][CH:19]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCOC(/N=N/C(OCC)=O)=O>CCOCC>[CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][CH2:15][O:16][C:21]2[CH:22]=[CH:23][C:18]([F:17])=[CH:19][CH:20]=2)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 97324-FluorophenolHCID 11776TriphenylphosphineHCID 27250292-(1-Benzylpiperidin-4-yl)ethanolHCID 5462977Diethyl azodicarboxylate

Product 1

HCID 99268361-Benzyl-4-(2-(4-fluorophenoxy)ethyl)piperidineYield 39.7%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Procedure

To a solution of 1.5 g (6.84 mmol) of 1-benzyl-4-(2-hydroxy-1-ethyl)piperidine (Acros Chemical), 3.8 g (34.2 mmol) of 4-fluorophenol and 3.6 g (13.7 mmol) of triphenylphosphine in 25 mL of ether at 0° C. was slowly added dropwise 2.15 mL (13.7 mmol) of diethylazodicarboxylate (DEAD). The reaction mixture was allowed to warm to rt and was stirred for 12 h. To the reaction mixture was added 70 mL of ether and it was filtered through a thin pad of celite. The filtrate was washed with sat'd Na2CO3 solution and sat's NaCl solution. It was dried over MgSO4, filtered and the filtrate concentrated. The residue was purified by chromatography (silica, hexanes: ethyl acetate, 4:1) to give 0.85 g of the title compound.

Workup

  1. filtrationwas filtered through a thin pad of celite
  2. washThe filtrate was washed with sat'd Na2CO3 solution
  3. dry with materialIt was dried over MgSO4
  4. filtrationfiltered
  5. concentrationthe filtrate concentrated
  6. customThe residue was purified by chromatography (silica, hexanes: ethyl acetate, 4:1)

Sources & evidence

ORD record
ord-887dd1f3c5de462d8d2507ea0868b756
Source dataset
uspto-grants-2001_10
Patent number
US06303593B1

Reaction notes

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