Trimethyl orthoacetate → Benzoxazole, 6-bromo-4-fluoro-2-methyl-

HRID 1487679Notes

Reaction equation

HRID 1487679 reaction equation
[NH2:1][C:2]1[C:7]([F:8])=[CH:6][C:5]([Br:9])=[CH:4][C:3]=1[OH:10].FC(F)(F)S([O-])(=O)=O.[Yb+3].FC(F)(F)S([O-])(=O)=O.FC(F)(F)S([O-])(=O)=O.[C:36](OC)(OC)(OC)[CH3:37]>CCO>[Br:9][C:5]1[CH:6]=[C:7]([F:8])[C:2]2[N:1]=[C:36]([CH3:37])[O:10][C:3]=2[CH:4]=1

Participants

5

Reactant 3

HCID 15050Trimethyl orthoacetateHCID 2733225Ytterbium triflateHCID 857118462-Amino-5-bromo-3-fluorophenol

Product 1

HCID 86726505Benzoxazole, 6-bromo-4-fluoro-2-methyl-Yield 73%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 2-amino-5-bromo-3-fluorophenol (1 equiv), ytterbium(iii) trifluoromethanesulfonate (0.01 equiv), and trimethyl orthoacetate (1.2 equiv) in EtOH (1.3 M) was heated to 90° C. for 2 h. The reaction mixture was filtered through celite and washed with EtOH. The residual filtrate was concentrated in vacuo, then saturated aqueous sodium bicarbonate added and extracted with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified using silica gel chromatography (0 to 60% ethyl acetate in hexane) to afford the title compound (73% yield). MS (ESI) m/z 232.2 [M+H]+.

Workup

  1. filtrationThe reaction mixture was filtered through celite
  2. washwashed with EtOH
  3. concentrationThe residual filtrate was concentrated in vacuo
  4. additionsaturated aqueous sodium bicarbonate added
  5. extractionextracted with ethyl acetate
  6. dry with materialThe combined organic layers were dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified

Sources & evidence

ORD record
ord-b12c419a9dea4b99897c3a7593e26e23
Source dataset
uspto-grants-2016_08
Patent number
US09428509B2

Reaction notes

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