Hydrochloric Acid → HCID 42633438, compound

HRID 2388236Notes

Reaction equation

HRID 2388236 reaction equation
[CH2:1]([C:8]1[C:13]2[C:14]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)=[N:15][O:16][C:12]=2[C:11]([OH:23])=[C:10]([C:24](OCC)=[O:25])[N:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:29][CH2:30][C:31]([OH:33])=[O:32].[O-]CC.[Na+].Cl>CN(C=O)C.C(=O)(O)[O-].[Na+].CCOC(C)=O.O>[CH2:1]([C:8]1[C:13]2[C:14]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)=[N:15][O:16][C:12]=2[C:11]([OH:23])=[C:10]([C:24]([NH:29][CH2:30][C:31]([OH:33])=[O:32])=[O:25])[N:9]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 750GlycineHCID 2723922Sodium ethoxideHCID 67529900HCID 67529900, compound

Product 1

HCID 42633438HCID 42633438, compoundYield 67.1%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Procedure

Ethyl 4-benzyl-7-hydroxy-3-phenylisoxazolo[4,5-c]pyridine-6-carboxylate (36 mg, 0.096 mmol), glycine (145 mg, 1.93 mmol), sodium ethoxide (98 mg, 1.44 mmol) in 3 mL of DMF were refluxed for 2 h. After cooling to room temperature, water (15 mL) and EtOAc (20 mL) were added. The mixture was acidified to pH 2 by addition of 4M hydrochloric acid. The aqueous layer was extracted with additional EtOAc and the combined organic layer was dried over MgSO4. After evaporation of solvent, the residue was redissolved in EtOAc and washed several times with water to remove residual DMF. Drying over MgSO4 followed by evaporation afforded 28 mg of crude solid. The solid was dissolved in 50 mL of saturated sodium bicarbonate solution and washed with hexanes and EtOAc. The aqueous layer was acidified to pH 2 with 4M hydrochloric acid and extracted with EtOAc. The organic layer was dried over MgSO4 and concentrated to give 26 mg of the title compound. MS: (+) m/z 404.33 (M+1).

Workup

  1. extractionThe aqueous layer was extracted with additional EtOAc
  2. dry with materialthe combined organic layer was dried over MgSO4
  3. customAfter evaporation of solvent
  4. dissolutionthe residue was redissolved in EtOAc
  5. washwashed several times with water
  6. customto remove residual DMF
  7. dry with materialDrying over MgSO4
  8. customfollowed by evaporation
  9. customafforded 28 mg of crude solid
  10. washwashed with hexanes and EtOAc
  11. extractionextracted with EtOAc
  12. dry with materialThe organic layer was dried over MgSO4
  13. concentrationconcentrated

Sources & evidence

ORD record
ord-c3ca43f4dc0c44139adf1268cd72d4f9
Source dataset
uspto-grants-2012_09
Patent number
US08269008B2

Reaction notes

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