Ethanol → ethyl {3-[(2R)-2-((2R)-2-hydroxy-2-pyridin-3-ylethylamino)propyl]-1H-indol-7-yloxy}acetate

HRID 1351954Notes

Reaction equation

HRID 1351954 reaction equation
[OH:1][C@H:2]([C:22]1[CH:23]=[N:24][CH:25]=[CH:26][CH:27]=1)[CH2:3][NH:4][C@H:5]([CH3:21])[CH2:6][C:7]1[C:15]2[C:10](=[C:11]([O:16][CH2:17][C:18]([OH:20])=[O:19])[CH:12]=[CH:13][CH:14]=2)[NH:9][CH:8]=1.S(=O)(=O)(O)O.[CH2:33](O)[CH3:34]>>[OH:1][C@H:2]([C:22]1[CH:23]=[N:24][CH:25]=[CH:26][CH:27]=1)[CH2:3][NH:4][C@H:5]([CH3:21])[CH2:6][C:7]1[C:15]2[C:10](=[C:11]([O:16][CH2:17][C:18]([O:20][CH2:33][CH3:34])=[O:19])[CH:12]=[CH:13][CH:14]=2)[NH:9][CH:8]=1

Participants

4

Reactant 3

HCID 702EthanolHCID 1118Sulfuric AcidHCID 9848117{3-[(2R)-2-((2R)-2-Hydroxy-2-pyridin-3-ylethylamino)propyl]-1H-indol-7-yloxy}acetic acid

Product 1

HCID 86604027ethyl {3-[(2R)-2-((2R)-2-hydroxy-2-pyridin-3-ylethylamino)propyl]-1H-indol-7-yloxy}acetate

Procedure

{3-[(2R)-2-((2R)-2-Hydroxy-2-pyridin-3-ylethylamino)propyl]-1H-indol-7-yloxy}acetic acid (65 mg, 0.176 mmol) is dissolved in ethanol (5 mL), and thereto are added conc. sulfuric acid (0.1 mL) and Molecular Sieves 4A powder (trade name, 0.3 g), and the mixture is refluxed for 20 hours. After cooling, the insoluble materials are removed by filtration, and a saturated aqueous sodium hydrogen carbonate solution is added to the filtrate. The mixture is evaporated under reduced pressure to remove ethanol, and extracted with ethyl acetate. The organic layer is washed with a saturated brine, dried over sodium sulfate, and concentrated. The residue is purified by silica gel column chromatography (ethanol/chloroform=1/5→1/1). The obtained purified product is dissolved in ethanol (3 mL), and thereto is added 1N HCl/diethyl ether (0.5 mL). The mixture is concentrated under reduced pressure to give the desired ethyl {3-[(2R)-2-((2R)-2-hydroxy-2-pyridin-3-ylethylamino)propyl]-1H-indol-7-yloxy}acetate.2 hydrochloride (63 mg, yield: 76%).

Workup

  1. temperaturethe mixture is refluxed for 20 hours
  2. temperatureAfter cooling
  3. customthe insoluble materials are removed by filtration
  4. additiona saturated aqueous sodium hydrogen carbonate solution is added to the filtrate
  5. customThe mixture is evaporated under reduced pressure
  6. customto remove ethanol
  7. extractionextracted with ethyl acetate
  8. washThe organic layer is washed with a saturated brine
  9. dry with materialdried over sodium sulfate
  10. concentrationconcentrated
  11. customThe residue is purified by silica gel column chromatography (ethanol/chloroform=1/5→1/1)
  12. customThe obtained purified product
  13. dissolutionis dissolved in ethanol (3 mL)
  14. additionis added 1N HCl/diethyl ether (0.5 mL)
  15. concentrationThe mixture is concentrated under reduced pressure

Sources & evidence

ORD record
ord-f47b84e63cd84364aa8b481813435da2
Source dataset
uspto-grants-2007_05
Patent number
US07217724B2

Reaction notes

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