Phenol → 3-Bromo-5-phenoxypyridine

HRID 1507085Notes

Reaction equation

HRID 1507085 reaction equation
Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Br:8])[CH:7]=1.[C:9]1([OH:15])[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1>CN1C(=O)CCC1>[Br:8][C:6]1[CH:5]=[N:4][CH:3]=[C:2]([O:15][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH:7]=1

Participants

4

Reactant 2

HCID 996PhenolHCID 693693,5-Dibromopyridine

Product 1

HCID 232635923-Bromo-5-phenoxypyridineYield 50.5%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 3,5-dibromopyridine (XXXVII) (1.00 g, 4.24 mmol) in NMP (11 mL) was added phenol (XXXVIII) (398 mg, 4.24 mmol) and CsCO3 (1.38 g, 4.24 mmol). The reaction was heated at 100° C. over the weekend. The reaction was then partitioned between Et2O/water. The Et2O was separated, washed with 2× water, brine, dried over MgSO4 and concentrated under vacuum. The residue was purified on a silica gel column (100% hexanes→2:98 EtOAc:hexanes) to afford 3-bromo-5-phenoxypyridine (XXXIX) (535 mg, 2.14 mmol, 50% yield) as a clear oil. 1H NMR (DMSO-d6) δ ppm 7.13-7.15 (m, 2H), 7.23-7.26 (m, 1H), 7.43-7.46 (m, 2H), 7.69-7.70 (m, 1H), 8.37 (d, J=3 Hz, 1H), 8.49 (d, J=2 Hz, 1H); ESIMS found for C11H8BrNO m/z 250 (M+H).

Workup

  1. customThe reaction was then partitioned between Et2O/water
  2. customThe Et2O was separated
  3. washwashed with 2× water, brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated under vacuum
  6. customThe residue was purified on a silica gel column (100% hexanes→2:98 EtOAc:hexanes)

Sources & evidence

ORD record
ord-0614068de4b944129c1c9f922a19f1af
Source dataset
uspto-grants-2015_12
Patent number
US09221793B2

Reaction notes

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