Methanol → 5-(2-Benzyloxy-phenyl)-isoxazole-3-carboxylic acid

HRID 1093642Notes

Reaction equation

HRID 1093642 reaction equation
C([O:3][C:4]([C:6]1[CH:10]=[C:9]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[O:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[O:8][N:7]=1)=[O:5])C.CO.[OH-].[Na+]>C1COCC1.O>[CH2:18]([O:17][C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=1[C:9]1[O:8][N:7]=[C:6]([C:4]([OH:5])=[O:3])[CH:10]=1)[C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1

Participants

6

Reactant 3

HCID 887MethanolHCID 14798Sodium HydroxideHCID 665922385-(2-Benzyloxy-phenyl)-isoxazole-3-carboxylic acid ethyl ester

Product 1

HCID 548467765-(2-Benzyloxy-phenyl)-isoxazole-3-carboxylic acidYield 98.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

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. customVolatiles were removed by evaporation
  2. additionthe residue was diluted with water
  3. customThe resulting precipitate was isolated by filtration
  4. customdried

Sources & evidence

ORD record
ord-ffa46a2e20f6477c94fbc4ed6ff2528e
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

Loading…