Dimethylformamide → N-[2-Fluoro-6-(2-oxiranylmethoxy)phenyl]acetamide

HRID 490324Notes

Reaction equation

HRID 490324 reaction equation
N[C:2]1[C:7](F)=CC=C[C:3]=1[OH:9].[F:10][C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([OH:17])[C:12]=1[NH:18][C:19](=[O:21])[CH3:20].C(=O)([O-])[O-].[K+].[K+].CN(C=O)C>O.CO.C(OCC)(=O)C.O>[F:10][C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([O:17][CH2:7][CH:2]2[CH2:3][O:9]2)[C:12]=1[NH:18][C:19](=[O:21])[CH3:20]

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 27827782-amino-3-fluorophenol2×HCID 22386966N-(2-fluoro-6-hydroxyphenyl)acetamide

Product 1

HCID 22386963N-[2-Fluoro-6-(2-oxiranylmethoxy)phenyl]acetamideYield 45.8%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 22242641Methanol--water (1/1)Solvent

Conditions

Temperature
70 °C

Procedure

To a stirred solution of 2-amino-3-fluorophenol (300 mg, 2.36 mmol) in water-methanol (10 ml) acetic acid anhydride was added until all 2-amino-3-fluorophenol was consumed. The solution was concentrated to a residue of N-(2-fluoro-6-hydroxyphenyl) acetamide. To a mixture of N-(2-fluoro-6-hydroxyphenyl)acetamide (399 mg, 2.366 mmol) and potassium carbonate (652 mg, 4.72 mmol) in DMF (5 ml) epibromohydrin (388 mg, 2.8 mmol) was added and the mixture was stirred at 70° C. for 3 hr. Water and ethyl acetate were added, the organic phase separated, dried and concentrated. The resulting residue was purified by RP-HPLC (10-40% CH3CN) to give the desired product as a solid (242 mg, 1.08 mmol).

Workup

  1. customwas consumed
  2. concentrationThe solution was concentrated to a residue of N-(2-fluoro-6-hydroxyphenyl) acetamide
  3. additionwas added
  4. customthe organic phase separated
  5. customdried
  6. concentrationconcentrated
  7. customThe resulting residue was purified by RP-HPLC (10-40% CH3CN)

Sources & evidence

ORD record
ord-04b6fcb7c1f4483386e197979a078ce2
Source dataset
uspto-grants-2009_05
Patent number
US07528156B2

Reaction notes

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