Triethylamine → HCID 9885020, compound

HRID 1884576Notes

Reaction equation

HRID 1884576 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:25]=[CH:26][CH:27]=1)[O:5][C:6]1[C:11]([O:12][CH2:13][CH2:14][CH2:15][C:16]2[CH:21]=[CH:20][N:19]=[CH:18][C:17]=2C(O)=O)=[CH:10][CH:9]=[CH:8][N:7]=1.C1(P([N:42]=[N+]=[N-])(C2C=CC=CC=2)=O)C=CC=CC=1.C(N(CC)CC)C>C(O)(C)(C)C>[Cl:1][C:2]1[CH:3]=[C:4]([CH:25]=[CH:26][CH:27]=1)[O:5][C:6]1[C:11]([O:12][CH2:13][CH2:14][CH2:15][C:16]2[CH:21]=[CH:20][N:19]=[CH:18][C:17]=2[NH2:42])=[CH:10][CH:9]=[CH:8][N:7]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 12986045HCID 12986045, compound

Product 1

HCID 9885020HCID 9885020, compoundYield 49.7%

Reagents, catalysts & solvents 1

HCID 6386tert-ButanolSolvent

Conditions

Temperature
25 °C

Procedure

2-(3-Chlorophenoxy)-3-[3-(3-carboxypyridin-4-yl)propoxy]-pyridine (0.50 g, 1.3 mmol) obtained in Example 24 is dissolved in tert-butanol (20 ml), and thereto are added diphenylphosphoryl azide (0.42 ml, 2.0 mmol) and triethylamine (0.27 ml, 2.0 mmol), and the mixture is heated under reflux for 8 hours. The reaction is quenched with a saturated brine (50 ml), and the reaction solution is extracted with ethyl acetate (50 ml×2). The organic layer is washed with a saturated brine (30 ml×2), dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue is dissolved in methylene chloride (10 ml), and thereto is added trifluoroacetic acid (5 ml), and the mixture is stirred at 25° C. for 30 minutes. The reaction solution is concentrated under reduced pressure, and to the residue is added a saturated aqueous sodium hydrogen carbonate solution (50 ml), and the mixture is extracted with ethyl acetate (50 ml×2). The organic layer is washed with a saturated brine (30 ml×2), dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue is purified by silica gel column chromatography (eluent; chloroform/methanol), and further recrystallized from diethyl ether to give the title compound (0.23 g) as colorless crystals, m.p. 140-142° C.

Workup

  1. temperaturethe mixture is heated
  2. temperatureunder reflux for 8 hours
  3. customThe reaction is quenched with a saturated brine (50 ml)
  4. extractionthe reaction solution is extracted with ethyl acetate (50 ml×2)
  5. washThe organic layer is washed with a saturated brine (30 ml×2)
  6. dry with materialdried over anhydrous magnesium sulfate
  7. concentrationconcentrated under reduced pressure
  8. dissolutionThe residue is dissolved in methylene chloride (10 ml)
  9. additionis added trifluoroacetic acid (5 ml)
  10. concentrationThe reaction solution is concentrated under reduced pressure
  11. additionto the residue is added a saturated aqueous sodium hydrogen carbonate solution (50 ml)
  12. extractionthe mixture is extracted with ethyl acetate (50 ml×2)
  13. washThe organic layer is washed with a saturated brine (30 ml×2)
  14. dry with materialdried over anhydrous magnesium sulfate
  15. concentrationconcentrated under reduced pressure
  16. customThe residue is purified by silica gel column chromatography (eluent; chloroform/methanol)
  17. customfurther recrystallized from diethyl ether

Sources & evidence

ORD record
ord-cd207b008eb3405484327ac94e289820
Source dataset
uspto-grants-2004_07
Patent number
US06765095B2

Reaction notes

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