Methyl 2-amino-6-fluoro-3-hydroxybenzoate → Methyl 2-amino-5-fluorobenzoxazole-4-carboxylate

HRID 249922

Reaction equation

HRID 249922 reaction equation
[NH2:1][C:2]1[C:11]([OH:12])=[CH:10][CH:9]=[C:8]([F:13])[C:3]=1[C:4]([O:6][CH3:7])=[O:5].[N:14]1(C(N2C=CN=C2)N)C=CN=[CH:15]1>C1COCC1>[NH2:14][C:15]1[O:12][C:11]2[C:2](=[C:3]([C:4]([O:6][CH3:7])=[O:5])[C:8]([F:13])=[CH:9][CH:10]=2)[N:1]=1

Participants

4

Reactant 2

HCID 66873679Methyl 2-amino-6-fluoro-3-hydroxybenzoateHCID 66874404di(1H-imidazole-1-yl)methanamine

Product 1

HCID 66873993Methyl 2-amino-5-fluorobenzoxazole-4-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of methyl 2-amino-6-fluoro-3-hydroxybenzoate (0.4 g, 2.2 mmol) in THF (10 mL) was added di-(1H-imidazole-1-yl)methanamine (0.44 g, 2.75 mmol) at room temperature and the resulting reaction mixture was heated at reflux for 16 h. The reaction mixture cooled to room temperature and was concentrated under reduced pressure. The residue was dissolved in CH2Cl2 (100 mL), and the solution was treated with saturated aqueous ammonium chloride (25 mL). The organic layer was separated and the aqueous layer was extracted with additional CH2Cl2 (2×100 mL). The combined organic phase was washed with brine (2×100 mL), dried (Na2SO4), filtered, and concentrated under reduced pressure to afford a yellow solid. The solid was triturated from ether to afford methyl 2-amino-5-fluorobenzoxazole-4-carboxylate. MS consistent.

Workup

  1. customthe resulting reaction mixture
  2. temperaturewas heated
  3. temperatureat reflux for 16 h
  4. concentrationwas concentrated under reduced pressure
  5. dissolutionThe residue was dissolved in CH2Cl2 (100 mL)
  6. additionthe solution was treated with saturated aqueous ammonium chloride (25 mL)
  7. customThe organic layer was separated
  8. extractionthe aqueous layer was extracted with additional CH2Cl2 (2×100 mL)
  9. washThe combined organic phase was washed with brine (2×100 mL)
  10. dry with materialdried (Na2SO4)
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure
  13. customto afford a yellow solid
  14. customThe solid was triturated from ether

Sources & evidence

ORD record
ord-eaa3a55acb134139bc55aedf3f9b9501
Source dataset
uspto-grants-2011_01
Patent number
US07863271B2

Linked notes

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