Acetyl chloride → 2-Methyl-1,3-benzoxazole-4-carboxylic acid

HRID 1987992

Reaktionsgleichung

Reaktionsgleichung von HRID 1987992
Br.[NH2:2][C:3]1[C:11]([OH:12])=[CH:10][CH:9]=[CH:8][C:4]=1[C:5]([OH:7])=[O:6].[C:13](Cl)(=O)[CH3:14].C(N(CC)CC)C.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>ClCCl.O>[CH3:13][C:14]1[O:12][C:11]2[C:3](=[C:4]([C:5]([OH:7])=[O:6])[CH:8]=[CH:9][CH:10]=2)[N:2]=1

Komponenten

7

Edukt 4

HCID 6367Acetyl chlorideHCID 8471TriethylamineHCID 521998p-Toluenesulfonic acid monohydrateHCID 668807402-Amino-3-hydroxybenzoic acid hydrobromide

Produkt 1

HCID 183546282-Methyl-1,3-benzoxazole-4-carboxylic acidAusbeute 64 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

To a mixture of 2-amino-3-hydroxybenzoic acid hydrobromide (0.35 g, 1.50 mmol) and acetyl chloride (0.11 mL, 1.50 mmol) in dichloromethane (10 mL) was added triethylamine (0.84 mL, 6.0 mmol) dropwise, then the reaction mixture was stirred at room temperature for 12 h. The reaction mixture was diluted with dichloromethane, and then washed with 2 N HCl. The aqueous layer was extracted with dichloromethane. The combined organic layers were washed with brine, dried (Na2SO4), filtered and concentrated. The crude product was dissolved in toluene (10 mL) and the solution was treated with p-toluenesulfonic acid monohydrate (263 mg, 1.38 mmol). The reaction mixture was then heated to reflux for 1.5 h. The reaction was cooled to room temperature, poured into water and extracted with ethyl acetate. The organic layer was separated then washed with water, brine, dried (Na2SO4), filtered and concentrated. The crude product was purified by column chromatography (silica gel, 9:1 to 3:1 ethyl acetate/methanol) to afford 2-methylbenzoxazole-4-carboxylic acid (0.17 g, 64%) as an off-white solid: MS (ESI+) m/z 178 (M+H).

Aufarbeitung

  1. washwashed with 2 N HCl
  2. extractionThe aqueous layer was extracted with dichloromethane
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. dissolutionThe crude product was dissolved in toluene (10 mL)
  8. temperatureThe reaction mixture was then heated
  9. temperatureto reflux for 1.5 h
  10. temperatureThe reaction was cooled to room temperature
  11. extractionextracted with ethyl acetate
  12. customThe organic layer was separated
  13. washthen washed with water, brine
  14. dry with materialdried (Na2SO4)
  15. filtrationfiltered
  16. concentrationconcentrated
  17. customThe crude product was purified by column chromatography (silica gel, 9:1 to 3:1 ethyl acetate/methanol)

Quellen und Nachweise

ORD-Eintrag
ord-20f3a9151b214a2dae58ea1923ec61a8
Quelldatensatz
uspto-grants-2009_06
Patentnummer
US07553846B2

Verknüpfte Notizen

Wird geladen…