Sodium Hydroxide → 2-Methoxyoxazole-5-carboxylic acid

HRID 2384111Notes

Reaction equation

HRID 2384111 reaction equation
Cl[C:2]1[O:3][C:4]([C:7]([O:9]CC)=[O:8])=[CH:5][N:6]=1.[CH3:12][O-:13].[Na+].[OH-].[Na+]>CC#N.CO>[CH3:12][O:13][C:2]1[O:3][C:4]([C:7]([OH:9])=[O:8])=[CH:5][N:6]=1

Participants

6

Reactant 3

HCID 14798Sodium HydroxideHCID 10942334Sodium MethoxideHCID 26369855Ethyl 2-chloro-1,3-oxazole-5-carboxylate

Product 1

HCID 553038672-Methoxyoxazole-5-carboxylic acidYield 69.9%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 6342AcetonitrileSolvent

Procedure

To a solution of ethyl 2-chlorooxazole-5-carboxylate (510 mg, 2.90 mmol) in anhdryous MeCN (10 mL) and anhydrous MeOH (10 mL) is added NaOMe (628 mg, 11.62 mmol). The crude is stirred at reflux for 2 hrs. To this crude is added additional MeOH. The crude is refluxed for another 4 hrs. The crude is cooled and then concentrated and is redissolved in MeOH (10 mL). To this crude is added 1 N NaOH (10 ml, 10 mmol). The crude is stirred at room temperature for 3 hrs. The crude is quenched with concentrated HCl, PH adjusted to 7 via pH paper indicator. The crude is concentrated to remove MeOH. The crude is diluted in water. The aq. layer is acidified with concentrated HCl and diluted in EtOAc. The organic layer is washed with water, brine, dried over MgSO4, filtered, and concentrated to give 2-methoxyoxazole-5-carboxylic acid (290 mg). This acid is used without further purification. HPLC retention time=0.58 minutes (condition B); MS 144.0 (M+1).

Workup

  1. temperatureat reflux for 2 hrs
  2. temperatureThe crude is refluxed for another 4 hrs
  3. temperatureThe crude is cooled
  4. concentrationconcentrated
  5. dissolutionis redissolved in MeOH (10 mL)
  6. stirringThe crude is stirred at room temperature for 3 hrs
  7. customThe crude is quenched with concentrated HCl, PH
  8. concentrationThe crude is concentrated
  9. customto remove MeOH
  10. additionThe crude is diluted in water
  11. additiondiluted in EtOAc
  12. washThe organic layer is washed with water, brine
  13. dry with materialdried over MgSO4
  14. filtrationfiltered
  15. concentrationconcentrated

Sources & evidence

ORD record
ord-dfa35e1af54f45cdbe39a1778e192a4f
Source dataset
uspto-grants-2012_09
Patent number
US08263629B2

Reaction notes

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