1-Hydroxybenzotriazole → 2-[(5-Phenyl-1,2-oxazol-3-yl)formamido]acetic acid

HRID 1093582Notes

Reaction equation

HRID 1093582 reaction equation
C1(C2ON=C(C(O)=O)C=2)C=CC=CC=1.CCN(C(C)C)C(C)C.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.Cl.C(OC(=O)CN)C.C([O:56][C:57](=[O:73])[CH2:58][NH:59][C:60]([C:62]1[CH:66]=[C:65]([C:67]2[CH:72]=[CH:71][CH:70]=[CH:69][CH:68]=2)[O:64][N:63]=1)=[O:61])C.O[Li].O>CN(C=O)C.O.C1COCC1.CO>[C:67]1([C:65]2[O:64][N:63]=[C:62]([C:60]([NH:59][CH2:58][C:57]([OH:73])=[O:56])=[O:61])[CH:66]=2)[CH:68]=[CH:69][CH:70]=[CH:71][CH:72]=1

Participants

12

Reactant 7

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 1519165-Phenyl-3-isoxazolecarboxylic acidHCID 168937Lithium hydroxide, monohydrateHCID 2723640Glycine ethyl ester, hydrochlorideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 60484361HCID 60484361, compound

Product 1

HCID 433543392-[(5-Phenyl-1,2-oxazol-3-yl)formamido]acetic acidYield 85.7%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolvent2×HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 5-phenyl-isoxazole-3-carboxylic acid (1 g, 0.00529 mol) in DMF (5 mL) was added DIPEA (2.73 g, 0.0211 mol), HOBt (0.89 g, 0.006078 mol) and EDCI.HCl (1.266 g, 0.00661 mol) at ambient temperature. After 2 minutes glycine ethyl ester hydrochloride (0.811 g, 0.00581 mol) was added and the resulting mixture was stirred at ambient temperature overnight. The reaction mixture was diluted with cold water and the resulting precipitate was isolated by filtration and dried to afford 0.744 g (56%) of 5-phenyl-isoxazole-3-carbonyl)-amino]-acetic acid ethyl ester. LCMS: 275.1 (M+1)+, 94%. To a stirred solution of [(5-phenyl-isoxazole-3-carbonyl)-amino]-acetic acid ethyl ester (0.74 g, 0.00270 mol) in a mixture of THF (5 mL), methanol (5 mL) and H2O (5 mL) was added LiOH.H2O (0.34 g, 0.00809 mol) and the resulting mixture was stirred at ambient temperature for 1 hour. Volatiles were then evaporated and the resulting residue was diluted with water and acidified with concentrated HCl. The resulting precipitate was isolated by filtration and dried to afford 0.57 g (76%) of [(5-phenyl-isoxazole-3-carbonyl)-amino]-acetic acid. LCMS: 247.06 (M+1)+, 98.18%.

Workup

  1. customthe resulting precipitate was isolated by filtration
  2. customdried
  3. customto afford 0.744 g (56%) of 5-phenyl-isoxazole-3-carbonyl)-amino]-acetic acid ethyl ester
  4. stirringthe resulting mixture was stirred at ambient temperature for 1 hour
  5. customVolatiles were then evaporated
  6. additionthe resulting residue was diluted with water
  7. customThe resulting precipitate was isolated by filtration
  8. customdried

Sources & evidence

ORD record
ord-3c4f4604d31c45ce8e35cc238b67cd34
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

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