Pyridinium chloride → 2-(3-Bromophenoxy)-3-[3-(3-hydroxy-5-methoxypyridin-4-yl)propoxy]pyridine

HRID 1841570Notes

Reaction equation

HRID 1841570 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([CH:26]=[CH:27][CH:28]=1)[O:5][C:6]1[C:11]([O:12][CH2:13][CH2:14][CH2:15][C:16]2[C:21]([O:22]C)=[CH:20][N:19]=[CH:18][C:17]=2[O:24][CH3:25])=[CH:10][CH:9]=[CH:8][N:7]=1.Cl.N1C=CC=CC=1>C(=O)([O-])O.[Na+]>[Br:1][C:2]1[CH:3]=[C:4]([CH:26]=[CH:27][CH:28]=1)[O:5][C:6]1[C:11]([O:12][CH2:13][CH2:14][CH2:15][C:16]2[C:17]([O:24][CH3:25])=[CH:18][N:19]=[CH:20][C:21]=2[OH:22])=[CH:10][CH:9]=[CH:8][N:7]=1.[Br:1][C:2]1[CH:3]=[C:4]([CH:26]=[CH:27][CH:28]=1)[O:5][C:6]1[C:11]([O:12][CH2:13][CH2:14][CH2:15][C:16]2[C:17]([OH:24])=[CH:18][N:19]=[CH:20][C:21]=2[OH:22])=[CH:10][CH:9]=[CH:8][N:7]=1

Participants

5

Reactant 2

HCID 10176127Pyridinium chlorideHCID 15895874HCID 15895874, compound

Product 2

HCID 235062512-(3-Bromophenoxy)-3-[3-(3-hydroxy-5-methoxypyridin-4-yl)propoxy]pyridineHCID 235062562-(3-Bromophenoxy)-3-[3-(3,5-dihydroxypyridin-4-yl)propoxy]pyridine

Reagents, catalysts & solvents 1

HCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
180 °C

Procedure

A mixture of 2-(3-bromophenoxy)-3-[3-(3,5-dimethoxypyridin-4-yl)propoxy]pyridine (3.15 g, 7.1 mmol) obtained in Example 19 and pyridine hydrochloride (8.0 g) is stirred at 180° C. for 1.5 hours. After being allowed to cool, to the mixture is added a saturated aqueous sodium hydrogen carbonate solution (100 ml), and the mixture is extracted with ethyl acetate (100 ml×3). The organic layer is washed with a saturated brine (50 ml×2), dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue is purified by silica gel column chromatography (eluent: chloroform/methanol) to give 2-(3-bromophenoxy)-3-[3-(3-hydroxy-5-methoxy-pyridin-4-yl)propoxy]pyridine and 2-(3-bromophenoxy)-3-[3-(3,5-dihydroxypyridin-4-yl)propoxy]pyridine, which are individually treated with fumaric acid to give 2-(3-bromophenoxy)-3-[3-(3-hydroxy-5-methoxypyridin-4-yl)propoxy]pyridine.0.5 fumarate (1.00 g) [m.p. 157-161° C. (recrystallized from ethanol/diethyl ether)] and 2-(3-bromo-phenoxy)-3-[3-(3,5-dihydroxypyridin-4-yl)propoxy]pyridine.0.5 fumarate (1.36 g) [m.p. 184-189° C. (recrystallized from ethanol)], respectively.

Workup

  1. temperatureto cool, to the mixture
  2. extractionthe mixture is extracted with ethyl acetate (100 ml×3)
  3. washThe organic layer is washed with a saturated brine (50 ml×2)
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue is purified by silica gel column chromatography (eluent: chloroform/methanol)

Sources & evidence

ORD record
ord-bbaddaf29ce14ec39fb6505687d57596
Source dataset
uspto-grants-2004_01
Patent number
US06683186B2

Reaction notes

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