Pyridine → 4-Benzoxazolecarboxylic acid, 2-methyl-, methyl ester

HRID 2175720Notes

Reaction equation

HRID 2175720 reaction equation
[NH2:1][C:2]1[C:11]([OH:12])=[CH:10][CH:9]=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].[C:13](Cl)(=O)[CH3:14].C(N(CC)CC)C.N1C=CC=CC=1.CC1C=CC(S(O)(=O)=O)=CC=1>C1(C)C(C)=CC=CC=1.O>[CH3:13][C:14]1[O:12][C:11]2[C:2](=[C:3]([C:4]([O:6][CH3:7])=[O:5])[CH:8]=[CH:9][CH:10]=2)[N:1]=1

Participants

8

Reactant 5

HCID 1049PyridineHCID 6101p-Toluenesulfonic acidHCID 6367Acetyl chlorideHCID 8471TriethylamineHCID 205248Anthranilic acid, 3-hydroxy-, methyl ester

Product 1

HCID 146167624-Benzoxazolecarboxylic acid, 2-methyl-, methyl esterYield 79%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 7237O-XyleneSolvent

Procedure

A solution of methyl 2-amino-3-hydroxybenzoate (167 mg, 1.0 mmol), acetyl chloride (86 mg, 1.1 mmol) and triethylamine (101 mg, 1.1 mmol) in xylene (10 mL) was stirred at 0° C. for 2 h. Pyridine (20 mg, 0.25 mmol) and TsOH (43 mg, 0.25 mmol) were then added and the mixture was heated at reflux overnight. The mixture was then cooled to room temperature, diluted with water and extracted with ethyl acetate. The combined organic extracts were washed with water, brine, then dried over sodium sulfate and the solvent was removed under reduced pressure. The residue was purified by flash chromatography using petroleum ether/ethyl acetate 5:1 (v:v) as eluent to give methyl 2-methylbenzo[d]oxazole-4-carboxylate (151 mg, 79%). LC-MS (ES-API); rt 8.08 min; m/z calculated for C10H9NO3 [M+H]+ 192.1, found 192.1.

Workup

  1. temperaturethe mixture was heated
  2. temperatureat reflux overnight
  3. extractionextracted with ethyl acetate
  4. washThe combined organic extracts were washed with water, brine
  5. dry with materialdried over sodium sulfate
  6. customthe solvent was removed under reduced pressure
  7. customThe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-0ce664a699454f909607dab5067c060a
Source dataset
uspto-grants-2015_06
Patent number
US09062076B2

Reaction notes

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