Methanol → HCID 57874519, compound

HRID 1093644Notes

Reaction equation

HRID 1093644 reaction equation
C([O:3][C:4](=[O:28])[CH2:5][NH:6][C:7]([C:9]1[CH:13]=[C:12]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[O:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[O:11][N:10]=1)=[O:8])C.CO.O.O[Li].O>C1COCC1>[CH2:21]([O:20][C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=1[C:12]1[O:11][N:10]=[C:9]([C:7]([NH:6][CH2:5][C:4]([OH:28])=[O:3])=[O:8])[CH:13]=1)[C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 962WaterHCID 168937Lithium hydroxide, monohydrateHCID 66591653{[5-(2-Benzyloxy-phenyl)-isoxazole-3-carbonyl]-amino}-acetic acid ethyl ester

Product 1

HCID 57874519HCID 57874519, compoundYield 92.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 5-(2-benzyloxy-phenyl)-isoxazole-3-carboxylic acid (0.7 g, 0.00237 mol) in DMF (4 mL) was added DIPEA (1.226 g, 0.00948 mol), HOBt (0.4 g, 0.0029 mol) and EDCI.HCl (0.57 g, 0.0029 mol) at ambient temperature. After 5 minutes glycine ethyl ester hydrochloride (0.347 g, 0.0024 8 mol) was added and the resulting mixture was stirred overnight. The reaction mixture was then diluted with cold water and the resulting precipitate was isolated by filtration. Purification by column chromatography using silica gel 60-120 mesh (65% ethyl acetate in hexane) afforded 0.66 g (73%) of {[5-(2-benzyloxy-phenyl)-isoxazole-3-carbonyl]-amino}-acetic acid ethyl ester. To a stirred solution of {[5-(2-benzyloxy-phenyl)-isoxazole-3-carbonyl]-amino}-acetic acid ethyl ester (0.65 g, 0.00171 mol) in a mixture of THF (10 mL), methanol (5 mL) and H2O (5 mL) was added LiOH.H2O (0.215 g, 0.00512 mol) at ambient temperature. The resulting mixture was stirred overnight. 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 0.56 g of {[5-(2-benzyloxy-phenyl)-isoxazole-3-carbonyl]-amino}-acetic acid. LCMS: 353.11 (M+1)+, 60.4%.

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-387074b700164909b9aa0d12f13b44fd
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

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