Hydrochloric Acid → HCID 42633442, compound

HRID 2388252Notes

Reaction equation

HRID 2388252 reaction equation
C(O[C:4]([C:6]1[N:11]=[CH:10][C:9]2[C:12]([CH2:15][CH3:16])=[N:13][O:14][C:8]=2[C:7]=1[OH:17])=[O:5])C.[NH2:18][CH2:19][C:20]([OH:22])=[O:21].[O-]CC.[Na+].Cl>CN(C=O)C.O.CCOC(C)=O>[CH2:15]([C:12]1[C:9]2[CH:10]=[N:11][C:6]([C:4]([NH:18][CH2:19][C:20]([OH:22])=[O:21])=[O:5])=[C:7]([OH:17])[C:8]=2[O:14][N:13]=1)[CH3:16]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 750GlycineHCID 2723922Sodium ethoxideHCID 67530668HCID 67530668, compound

Product 1

HCID 42633442HCID 42633442, compoundYield 50.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

3-Ethyl-7-hydroxy-isoxazolo[4,5-c]pyridine-6-carboxylic acid ethyl ester (80 mg, 0.42 mmol) was dissolved in 12 mL of DMF. Glycine (0.51 g, 6.78 mmol) and sodium ethoxide (0.35 g, 5.08 mmol) were added and the mixture was refluxed for 2 h. The mixture was cooled to room temperature and diluted with 60 mL of water. EtOAc (50 mL) was added and the resulting biphasic mixture was stirred vigorously as 4M hydrochloric acid was added dropwise until pH was 3. The aqueous layer was extracted with additional EtOAc, and the combined organic layer was washed with water and dried over MgSO4. The solvent was evaporated and the solid residue was taken up in 50 mL of saturated sodium bicarbonate solution. The aqueous phase was washed with hexanes and EtOAc. The aqueous layer was then acidified to pH 2 by addition of concentrated hydrochloric acid and extracted with EtOAc (3×50 mL). The combined organic layer was dried over MgSO4 and concentrated to give 56 mg of the title compound. MS: (+) m/z 266.32 (M+1).

Workup

  1. temperaturethe mixture was refluxed for 2 h
  2. additionwas added dropwise until pH was 3
  3. extractionThe aqueous layer was extracted with additional EtOAc
  4. washthe combined organic layer was washed with water
  5. dry with materialdried over MgSO4
  6. customThe solvent was evaporated
  7. washThe aqueous phase was washed with hexanes and EtOAc
  8. additionThe aqueous layer was then acidified to pH 2 by addition of concentrated hydrochloric acid
  9. extractionextracted with EtOAc (3×50 mL)
  10. dry with materialThe combined organic layer was dried over MgSO4
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-0254e96a424d458d9b12d1eab69a23f0
Source dataset
uspto-grants-2012_09
Patent number
US08269008B2

Reaction notes

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