Ethanol → (S)-3-((3,4-Dimethoxyphenoxy)methyl)-5-(pyrrolidin-2-yl)isoxazole

HRID 710055Notes

Reaction equation

HRID 710055 reaction equation
CCO.[CH3:4][O:5][C:6]1[CH:7]=[C:8]([CH:27]=[CH:28][C:29]=1[O:30][CH3:31])[O:9][CH2:10][C:11](=O)[C:12]#[C:13][C@@H:14]1[CH2:18][CH2:17][CH2:16][N:15]1C(OC(C)(C)C)=O.Cl.[NH2:33][OH:34].C(O)(C(F)(F)F)=O>C(Cl)(Cl)Cl>[CH3:4][O:5][C:6]1[CH:7]=[C:8]([CH:27]=[CH:28][C:29]=1[O:30][CH3:31])[O:9][CH2:10][C:11]1[CH:12]=[C:13]([C@@H:14]2[CH2:18][CH2:17][CH2:16][NH:15]2)[O:34][N:33]=1

Participants

6

Reactant 4

HCID 702EthanolHCID 6422Trifluoroacetic acidHCID 443297Hydroxyamine hydrochlorideHCID 86706767(S)-t-Butyl 2-(4-(3,4-dimethoxyphenoxy)-3-oxobut-1-yn-1-yl)pyrrolidine-1-carboxylate

Product 1

HCID 86706768(S)-3-((3,4-Dimethoxyphenoxy)methyl)-5-(pyrrolidin-2-yl)isoxazoleYield 107%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

To an EtOH (10 mL) solution of the compound (390 mg) obtained in Example 14-(2), hydroxylamine hydrochloride (139 mg) was added and the mixture was heated under reflux for 20 hours. The reaction mixture was concentrated to give a brown oil, to which CHCl3 (1.0 mL) and TFA (5.0 mL) were added, followed by stirring at room temperature for 21 hours. After concentrating the reaction mixture, saturated aqueous sodium bicarbonate (50 mL) was added and the organic layer extracted with CHCl3 (50 mL×2) was dried (Na2SO4), filtered and concentrated to give the titled compound (326 mg, brown oil) as a mixture with impurities.

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux for 20 hours
  3. concentrationThe reaction mixture was concentrated
  4. customto give a brown oil
  5. concentrationAfter concentrating the reaction mixture, saturated aqueous sodium bicarbonate (50 mL)
  6. additionwas added
  7. extractionthe organic layer extracted with CHCl3 (50 mL×2)
  8. dry with materialwas dried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-f7bc19e6cdc142149fb45e5e3df92fec
Source dataset
uspto-grants-2015_11
Patent number
US09181229B2

Reaction notes

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