Oxalyl chloride → HCID 89443501, compound

HRID 1771707Notes

Reaction equation

HRID 1771707 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:11])=[C:6]([CH:10]=1)[C:7]([OH:9])=O.C(Cl)(C(Cl)=O)=O.[NH2:18][C:19]1[C:20]([F:27])=[C:21]([OH:26])[CH:22]=[CH:23][C:24]=1[F:25].C([O-])(O)=O.[Na+]>C(Cl)Cl.C1COCC1.O.CN(C=O)C>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:11])=[C:6]([CH:10]=1)[C:7]([NH:18][C:19]1[C:24]([F:25])=[CH:23][CH:22]=[C:21]([OH:26])[C:20]=1[F:27])=[O:9]

Participants

9

Reactant 4

HCID 65578Oxalyl chlorideHCID 516892Sodium BicarbonateHCID 27363155-Bromo-2-fluorobenzoic acidHCID 227559833-Amino-2,4-difluorophenol

Product 1

HCID 89443501HCID 89443501, compoundYield 79.9%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 5-bromo-2-fluoro-benzoic acid (5.1 g, 23.3 mmol, 1.0 eq) in CH2Cl2 (50 mL) were added (COCl)2 (8.8 g, 69.9 mmol, 3.0 eq) and DMF (0.07 mL). The reaction mixture was stirred at room temperature for 1.5 h then the solvent and excess reagent were removed under reduced pressure. The residue obtained was dissolved in THF (30 mL) and added dropwise to a mixture of 3-amino-2,4-difluorophenol (intermediate X(a)) (3.0 g, 20.9 mmol, 1.0 eq) and NaHCO3 (5.3 g, 62.9 mmol, 3.0 eq) in THF (3 mL) at 0° C. The reaction was allowed to warm to room temperature and stirred for 1 h then poured into water and extracted with EtOAc. The combined organic extracts were washed with water and brine, dried (Na2SO4), filtered and evaporated in vacuo. The residue obtained was purified by column chromatography (CH2Cl2:MeOH, 500:1 to 300:1) to give the title compound as a white solid (5.78 g 79%).

Workup

  1. customthe solvent and excess reagent were removed under reduced pressure
  2. customThe residue obtained
  3. temperatureto warm to room temperature
  4. stirringstirred for 1 h
  5. extractionextracted with EtOAc
  6. washThe combined organic extracts were washed with water and brine
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. customevaporated in vacuo
  10. customThe residue obtained
  11. customwas purified by column chromatography (CH2Cl2:MeOH, 500:1 to 300:1)

Sources & evidence

ORD record
ord-2f613bb5ddc146c59968a356dd32a278
Source dataset
uspto-grants-2016_02
Patent number
US09249085B2

Reaction notes

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