3-Hydroxyanthranilic Acid → Acetate

HRID 415190Notes

Reaction equation

HRID 415190 reaction equation
[OH:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:4]([C:5]([OH:7])=[O:6])[C:3]=1[NH2:11].[F:12][C:13]1[CH:21]=[CH:20][C:16]([C:17](Cl)=O)=[CH:15][CH:14]=1.N1C=CC=CC=1.Cl.CC1C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1.O.C(OCC)(=O)C>[C:5]([O-:7])(=[O:6])[CH3:4].[F:12][C:13]1[CH:21]=[CH:20][C:16]([C:17]2[O:1][C:2]3[C:3](=[C:4]([C:5]([OH:7])=[O:6])[CH:8]=[CH:9][CH:10]=3)[N:11]=2)=[CH:15][CH:14]=1

Participants

10

Reactant 5

HCID 863-Hydroxyanthranilic AcidHCID 313Hydrochloric AcidHCID 1049PyridineHCID 6101p-Toluenesulfonic acidHCID 678794-Fluorobenzoyl chloride

Product 2

HCID 175AcetateHCID 59626030HCID 59626030, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of 3-hydroxyanthranilic acid (0.153 g, 1.0 mmol) in toluene (10 mL) was added 4-fluorobenzoyl chloride (0.475 g, 3.0 mmol) followed by pyridine (0.275 g, 3.5 mmol) at room temperature. The resulting mixture was stirred at room temperature for 30 minutes then heated to 80° C. for 1 hr. After this time the reaction was cooled and poured into a mixture of ethyl acetate (50 mL) and 5% aqueous hydrochloric acid (20 mL). Subsequent separation of the layers, drying the organic over MgSO4 and filtration afforded a solution. After removal of the solvent, the residue was dissolved in toluene (20 mL) and the solution treated with 4-methylbenzenesulfonic acid (0.4 g, 2.1 mmol). The reaction mixture was then heated to reflux overnight. After this time the reaction was cooled and poured into water (100 mL), the organic layer was separated, washed with water (100 mL), dried over anhydrous magnesium sulfate and concentrated to give a solid. Re-crystallization of this solid from acetate gave 2-(4-fluorophenyl)benzo[d]oxazole-4-carboxylic acid as a white solid product (0.064 g, yield 24.9%). LC-MS (ESI) m/z 258 [M+1]+.

Workup

  1. temperaturethen heated to 80° C. for 1 hr
  2. temperatureAfter this time the reaction was cooled
  3. customSubsequent separation of the layers
  4. customdrying the
  5. filtrationorganic over MgSO4 and filtration
  6. customafforded a solution
  7. customAfter removal of the solvent
  8. dissolutionthe residue was dissolved in toluene (20 mL)
  9. temperatureThe reaction mixture was then heated
  10. temperatureto reflux overnight
  11. temperatureAfter this time the reaction was cooled
  12. customthe organic layer was separated
  13. washwashed with water (100 mL)
  14. dry with materialdried over anhydrous magnesium sulfate
  15. concentrationconcentrated
  16. customto give a solid

Sources & evidence

ORD record
ord-0bf5d1dc93f6420ab08a9250ba90c6a0
Source dataset
uspto-grants-2012_01
Patent number
US08088760B2

Reaction notes

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