Bis-(1H-imidazol-2-YL)-methanone → Methyl 2-oxo-2,3-dihydro-1,3-benzoxazole-6-carboxylate

HRID 590403Notes

Reaction equation

HRID 590403 reaction equation
[NH2:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][C:3]=1[OH:12].[C:13](C1NC=CN=1)(C1NC=CN=1)=[O:14]>C1COCC1>[O:14]=[C:13]1[NH:1][C:2]2[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][C:3]=2[O:12]1

Participants

4

Reactant 2

HCID 5250894Bis-(1H-imidazol-2-YL)-methanoneHCID 7020619Benzoic acid, 4-amino-3-hydroxy-, methyl ester2×

Product 1

HCID 12564532Methyl 2-oxo-2,3-dihydro-1,3-benzoxazole-6-carboxylateYield 56%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of methyl 4-amino-3-hydroxybenzoate (Intermediate 75, 1.06 g, 6.34 mmol) in THF (13.5 mL) was added carbonyl diimidazole (1.88 g, 11.6 mmol) and the reaction mixture was heated to reflux temperature for 1 day. After that time, the solvent was removed and the residue was partitioned between CH2Cl2 and 1N aqueous HCl solution. The organic phase was washed with 1N aqueous HCl solution (2×) and water, dried over anhydrous sodium sulphate, filtered and concentrated under reduced pressure to provide the title compound as white solid (870 mg of a 79% purity, 56% yield). The crude was used in the next step without any further purification.

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureto reflux temperature for 1 day
  3. customAfter that time, the solvent was removed
  4. customthe residue was partitioned between CH2Cl2 and 1N aqueous HCl solution
  5. washThe organic phase was washed with 1N aqueous HCl solution (2×) and water
  6. dry with materialdried over anhydrous sodium sulphate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-c0230705e94e4441bf756b5aa94ac744
Source dataset
uspto-grants-2016_01
Patent number
US09233108B2

Reaction notes

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