Potassium Carbonate → 1,3-Benzoxazole-4-carboxylic acid

HRID 249915Notes

Reaction equation

HRID 249915 reaction equation
Cl[C:2]1[O:3][C:4]2[C:5](=[C:7]([C:11]([O:13]C)=[O:12])[CH:8]=[CH:9][CH:10]=2)[N:6]=1.Cl.C[C@@H]1CSC[C@@H](C)N1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.O>[O:3]1[C:4]2=[CH:10][CH:9]=[CH:8][C:7]([C:11]([OH:13])=[O:12])=[C:5]2[N:6]=[CH:2]1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 56924368Methyl 2-chlorobenzo[d]oxazole-4-carboxylateHCID 86623723HCID 86623723, compound

Product 1

HCID 183546021,3-Benzoxazole-4-carboxylic acidYield 25.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
55 °C

Procedure

A mixture of methyl 2-chlorobenzoxazole-4-carboxylate (360 mg, 1.70 mmol), (3S,5S)/(3R,5R)-3,5-dimethylthiomorpholine hydrochloride (270 mg, 1.62 mmol) and potassium carbonate (672 mg, 4.86 mmol), in DMF (5 mL), was stirred at ambient temperature for 6 h. The reaction was then heated at 55° C. for 2 h before it was diluted with H2O (20 mL) and extracted with EtOAc (2×40 mL). The combined organic layers were washed with brine, dried (Na2SO4) and concentrated under reduced pressure. The crude methyl ester was retained for future purification. The remaining aqueous phase was then acidified to pH 5 by addition of 1 N HCl and extracted with CH2Cl2 (2×40 mL). The combined organic extracts were dried (Na2SO4) and concentrated under reduced pressure to afford crude (3S,5S)/(3R,5R)-3,5-dimethylthiomorpholino)benzoxazole-4-carboxylic acid (70 mg, 15%) which was directly elaborated without purification.

Workup

  1. extractionextracted with EtOAc (2×40 mL)
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated under reduced pressure
  5. customThe crude methyl ester was retained for future purification
  6. additionThe remaining aqueous phase was then acidified to pH 5 by addition of 1 N HCl
  7. extractionextracted with CH2Cl2 (2×40 mL)
  8. dry with materialThe combined organic extracts were dried (Na2SO4)
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-98389bc6e1ec4ba78068a62501fc0272
Source dataset
uspto-grants-2011_01
Patent number
US07863271B2

Reaction notes

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