Chloroform → 2-Phenoxy-3-[3-(3-(2-hydroxyethoxy)pyridin-4-yl)propoxy)pyridine

HRID 1841565Notes

Reaction equation

HRID 1841565 reaction equation
[H-].[Na+].[O:3]([C:10]1[C:15]([O:16][CH2:17][CH2:18][CH2:19][C:20]2[CH:25]=[CH:24][N:23]=[CH:22][C:21]=2[OH:26])=[CH:14][CH:13]=[CH:12][N:11]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.COC[O:30][CH2:31][CH2:32]Br.C(Cl)(Cl)Cl>CN(C=O)C>[O:3]([C:10]1[C:15]([O:16][CH2:17][CH2:18][CH2:19][C:20]2[CH:25]=[CH:24][N:23]=[CH:22][C:21]=2[O:26][CH2:32][CH2:31][OH:30])=[CH:14][CH:13]=[CH:12][N:11]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1

Participants

6

Reactant 4

HCID 6212ChloroformHCID 24758Sodium hydrideHCID 33310511-Bromo-2-(methoxymethoxy)ethaneHCID 98836252-Phenoxy-3-[3-(3-hydroxypyridin-4-yl)propoxy]pyridine

Product 1

HCID 235062262-Phenoxy-3-[3-(3-(2-hydroxyethoxy)pyridin-4-yl)propoxy)pyridine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Sodium hydride (60% in mineral oil, 0.08 g, 2.0 mmol) is suspended in DMF (5 ml), and thereto is added 2-phenoxy-3-[3-(3-hydroxypyridin-4-yl)propoxy]pyridine (0.20 g, 0.62 mmol) obtained in Example 30 at room temperature, and the mixture is stirred for 30 minutes. To the mixture is added 2-methoxymethoxyethyl bromide (0.32 g, 2.0 mmol) under ice-cooling, and the mixture is stirred at 50° C. for 30 minutes. To the reaction solution is added chloroform (100 ml), and the mixture is washed with a saturated brine (50 ml×2), dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. To the residue are added ethanol (20 ml) and a 35% aqueous hydrochloric acid solution (2 ml), and the mixture is stirred at 60° C. for 30 minutes. The pH value of the reaction solution is adjusted to pH 10 with a saturated aqueous sodium hydrogen carbonate solution, and the mixture is extracted with chloroform (50 ml×2), 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-phenoxy-3-[3-(3-(2-hydroxyethoxy)pyridin-4-yl)propoxy]pyridine, which is further treated with fumaric acid to give the title compound (0.17 g), m.p. 129-132° C. (recrystallized from ethanol/isopropyl ether).

Workup

  1. temperaturecooling
  2. stirringthe mixture is stirred at 50° C. for 30 minutes
  3. washthe mixture is washed with a saturated brine (50 ml×2)
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. additionTo the residue are added ethanol (20 ml)
  7. stirringa 35% aqueous hydrochloric acid solution (2 ml), and the mixture is stirred at 60° C. for 30 minutes
  8. extractionthe mixture is extracted with chloroform (50 ml×2)
  9. washwashed with a saturated brine (50 ml×2)
  10. dry with materialdried over anhydrous magnesium sulfate
  11. concentrationconcentrated under reduced pressure
  12. customThe residue is purified by silica gel column chromatography (eluent: chloroform/methanol)

Sources & evidence

ORD record
ord-9637abf59f85407d946a4baa1b67d428
Source dataset
uspto-grants-2004_01
Patent number
US06683186B2

Reaction notes

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