Hydroxyamine hydrochloride → 5-(2-Benzyloxy-phenyl)-isoxazole-3-carboxylic acid ethyl ester

HRID 1093641Notes

Reaction equation

HRID 1093641 reaction equation
[CH2:1]([O:3][C:4](=[O:24])[C:5](=O)[CH2:6][C:7]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[O:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[O:8])[CH3:2].Cl.[NH2:26]O>C(O)(=O)C>[CH2:1]([O:3][C:4]([C:5]1[CH:6]=[C:7]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[O:8][N:26]=1)=[O:24])[CH3:2]

Participants

4

Reactant 2

HCID 443297Hydroxyamine hydrochlorideHCID 12242179Ethyl 4-[2-(benzyloxy)phenyl]-2,4-dioxobutanoate

Product 1

HCID 665922385-(2-Benzyloxy-phenyl)-isoxazole-3-carboxylic acid ethyl esterYield 92.1%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

To a stirred solution of 4-(2-benzyloxy-phenyl)-2,4-dioxo-butyric acid ethyl ester (3.75 g, 0.01149 mole) in acetic acid (20 mL) was added hydroxylamine hydrochloride (0.878 g, 0.0126 mole) and the resulting mixture was heated to reflux for 3 hours. Volatiles were removed and the resulting residue was diluted with water, basified with sodium bicarbonate solution and extracted with ethyl acetate, washed the ethyl acetate with brine solution, dried over sodium sulfate and concentrated under reduced pressure to afford 3.42 g (92%) of 5-(2-benzyloxy-phenyl)-isoxazole-3-carboxylic acid ethyl ester. LCMS: 324.12 (M+1)+, 78.58%. To a stirred solution of 5-(2-benzyloxy-phenyl)-isoxazole-3-carboxylic acid ethyl ester (1.75 g, 0.00542 mol) in a mixture of THF (30 mL), methanol (15 mL) and H2O (15 mL) was added NaOH (0.651 g, 0.01628 mol) and the resulting mixture was stirred for 2 hours. The reaction mixture was then diluted with cold water. Volatiles were removed by evaporation and the residue was diluted with water acidified with concentrated HCl. The resulting precipitate was isolated by filtration and dried to afford 1.57 g (98%) of 5-(2-benzyloxy-phenyl)-isoxazole-3-carboxylic acid. LCMS: 296.08 (M+1)+, 84.73%

Workup

  1. temperaturethe resulting mixture was heated
  2. temperatureto reflux for 3 hours
  3. customVolatiles were removed
  4. additionthe resulting residue was diluted with water
  5. extractionextracted with ethyl acetate
  6. washwashed the ethyl acetate with brine solution
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-c47cce4193254c319fc74b7b0162f5b8
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

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