Triphenylphosphine → 2-(3-Bromophenoxy)-3-[3-(3-hydroxypyridin-4-yl)propoxy]pyridine

HRID 1267956Notes

Reaction equation

HRID 1267956 reaction equation
COC[O:4][C:5]1[CH:6]=[N:7][CH:8]=[CH:9][C:10]=1[CH2:11][CH2:12][CH2:13][OH:14].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.[Br:48][C:49]1[CH:50]=[C:51]([CH:60]=[CH:61][CH:62]=1)[O:52][C:53]1[C:58](O)=[CH:57][CH:56]=[CH:55][N:54]=1>C1COCC1>[Br:48][C:49]1[CH:50]=[C:51]([CH:60]=[CH:61][CH:62]=1)[O:52][C:53]1[C:58]([O:14][CH2:13][CH2:12][CH2:11][C:10]2[CH:9]=[CH:8][N:7]=[CH:6][C:5]=2[OH:4])=[CH:57][CH:56]=[CH:55][N:54]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 12986046HCID 12986046, compoundHCID 235062572-(3-Bromophenoxy)-3-pyridinol

Product 1

HCID 99528632-(3-Bromophenoxy)-3-[3-(3-hydroxypyridin-4-yl)propoxy]pyridineYield 82.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
40 °C

Procedure

3-(3-Methoxymethoxypyridin-4-yl)-1-propanol (2.50 g, 12.7 mmol) obtained in Example 2 and triphenylphosphine (4.50 g, 17.0 mmol) are dissolved in THF (40 ml), and thereto are successively added with stirring diisopropyl azodicarboxylate (3.00 g, 15.0 mmol) and 2-(3-bromophenoxy)-3-pyridinol (2.50 g, 9.4 mmol) obtained in Reference Example 11 under ice-cooling. The mixture is further stirred at 40° C. for 30 minutes, and the reaction solution is concentrated under reduced pressure. To the residue is added ethyl acetate (50 ml), and the mixture is extracted with a 10% aqueous hydrochloric acid solution (50 ml×2). The pH value of the aqueous layer is adjusted to pH 12 with potassium carbonate, and the mixture is extracted with ethyl acetate (100 ml×2). The organic layer 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 (200 ml) and a 47% aqueous hydrobromic acid solution (20 ml), and the mixture is heated under reflux for 30 minutes. The reaction solution is concentrated under reduced pressure, and neutralized with a saturated aqueous sodium hydrogen carbonate solution, and extracted with ethyl acetate (100 ml×2). 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: hexane/ethyl acetate/ethanol), recrystallized from ethanol/diethyl ether to give the title compound (3.10 g) as colorless crystals, m.p. 116-118° C.

Workup

  1. customobtained in Reference Example 11 under ice-
  2. temperaturecooling
  3. concentrationthe reaction solution is concentrated under reduced pressure
  4. additionTo the residue is added ethyl acetate (50 ml)
  5. extractionthe mixture is extracted with a 10% aqueous hydrochloric acid solution (50 ml×2)
  6. extractionthe mixture is extracted with ethyl acetate (100 ml×2)
  7. washThe organic layer is washed with a saturated brine (50 ml×2)
  8. dry with materialdried over anhydrous magnesium sulfate
  9. concentrationconcentrated under reduced pressure
  10. additionTo the residue are added ethanol (200 ml)
  11. temperaturea 47% aqueous hydrobromic acid solution (20 ml), and the mixture is heated
  12. temperatureunder reflux for 30 minutes
  13. concentrationThe reaction solution is concentrated under reduced pressure
  14. extractionextracted with ethyl acetate (100 ml×2)
  15. washThe organic layer is washed with a saturated brine (50 ml×2)
  16. dry with materialdried over anhydrous magnesium sulfate
  17. concentrationconcentrated under reduced pressure
  18. customThe residue is purified by silica gel column chromatography (eluent: hexane/ethyl acetate/ethanol)
  19. customrecrystallized from ethanol/diethyl ether

Sources & evidence

ORD record
ord-e4ce718daa30416ebbf9ece7db216f4f
Source dataset
uspto-grants-2003_04
Patent number
US06555557B1

Reaction notes

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