Phenol → 5-Bromo-2-(1-phenoxyethyl)pyridine

HRID 1501110Notes

Reaction equation

HRID 1501110 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]([OH:10])[CH3:9])=[N:6][CH:7]=1.[C:11]1(O)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>O1CCCC1>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]([O:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH3:9])=[N:6][CH:7]=1

Participants

6

Reactant 4

HCID 996PhenolHCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 426142881-(5-Bromopyridin-2-yl)ethanol

Product 1

HCID 895810635-Bromo-2-(1-phenoxyethyl)pyridineYield 94.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 1-(5-bromopyridin-2-yl)ethanol (1.0 g, 4.95 mmol), phenol (835 mg, 8.87 mmol), and triphenylphosphine (1.8 g, 6.86 mmol) was stirred in dry tetrahydrofuran (70 mL) at 0° C. under nitrogen atmosphere. To this mixture was added dropwise diisopropyl diazene-1,2-dicarboxylate (1.4 g, 6.92 mmol) over 5 minutes, and the reaction was monitored by thin layer chromatography. After complete disappearance of starting material, the solvent was removed under reduced pressure and the resultant oil was purified by flash column chromatography (hexane/ethyl acetate, 1/1) to give 5-bromo-2-(1-phenoxyethyl)pyridine (1.3 g, 94.4%) as a white solid. LRMS (M+H+) m/z: calcd 278.01. found 278 1H NMR (300 MHz, DMSO) δ 8.60 (d, J=2.1 Hz, 1H), 7.93 (dd, J1=8.4 Hz, J2=2.1 Hz, 1H), 7.41 (d, J=8.4 Hz, 1H), 7.18 (m, 2H), 6.86 (m, 3H), 5.39 (m, 1H), 1.63 (d, J=6.3 Hz, 3H).

Workup

  1. customAfter complete disappearance of starting material, the solvent was removed under reduced pressure
  2. customthe resultant oil was purified by flash column chromatography (hexane/ethyl acetate, 1/1)

Sources & evidence

ORD record
ord-a5ed972f73114138a8c02eb6836e222c
Source dataset
uspto-grants-2015_12
Patent number
US09206128B2

Reaction notes

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