Oxalyl chloride → HCID 89443673, compound

HRID 1771743Notes

Reaction equation

HRID 1771743 reaction equation
[F:1][C:2]1[CH:10]=[CH:9][C:8]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([F:17])[CH:12]=2)=[CH:7][C:3]=1[C:4]([OH:6])=O.C(Cl)(C(Cl)=O)=O.[NH2:24][C:25]1[C:26]([CH3:34])=[C:27]([OH:33])[CH:28]=[C:29]([CH3:32])[C:30]=1[F:31].C([O-])(O)=O.[Na+]>C(Cl)Cl.CN(C=O)C.C1COCC1.O>[F:1][C:2]1[CH:10]=[CH:9][C:8]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([F:17])[CH:12]=2)=[CH:7][C:3]=1[C:4]([NH:24][C:25]1[C:26]([CH3:34])=[C:27]([OH:33])[CH:28]=[C:29]([CH3:32])[C:30]=1[F:31])=[O:6]

Participants

9

Reactant 4

HCID 65578Oxalyl chlorideHCID 516892Sodium BicarbonateHCID 463123323',4-Difluoro-[1,1'-biphenyl]-3-carboxylic acidHCID 894436923-Amino-4-fluoro-2,5-dimethylphenol

Product 1

HCID 89443673HCID 89443673, compoundYield 65%

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 2-fluoro-5-(3-fluorophenyl)benzoic acid (Intermediate III(a)) (248 mg, 1.06 mmol, 1.1 eq) in CH2Cl2 (4 mL) and DMF (1 drop) at 0° C. was added (COCl)2 (403 mg, 3.18 mmol, 3.3 eq) dropwise. The reaction mixture was stirred at room temperature for 2 h. The solvent and excess reagent were then removed under reduced pressure and the residue obtained dissolved in THF (4 mL) and added dropwise to a mixture of 3-amino-4-fluoro-2,5-dimethylphenol (X(h)) (150 mg, 0.97 mmol, 1.0 eq) and NaHCO3 (407 mg, 4.85 mmol, 5.0 eq) in THF (3 mL) at 0° C. After the addition was completed, the reaction mixture was stirred at room temperature for 30 min. Water was added and the aqueous layer extracted with EtOAc. The organic extract was washed with aqueous NaHCO3, water and brine, dried (Na2SO4), filtered and evaporated in vacuo. The residue obtained was purified by column chromatography (petroleum ether:EtOAc, 6:1 to 5:1) to give an impure product. The crude material was triturated with a mixture of petroleum ether and EtOAc (3 mL:1 mL) and the solid collected by filtration to afforded the title compound as a white solid (233 mg, 65%).

Workup

  1. customThe solvent and excess reagent were then removed under reduced pressure
  2. customthe residue obtained
  3. additionAfter the addition
  4. stirringthe reaction mixture was stirred at room temperature for 30 min
  5. extractionthe aqueous layer extracted with EtOAc
  6. extractionThe organic extract
  7. washwas washed with aqueous NaHCO3, water and brine
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. customevaporated in vacuo
  11. customThe residue obtained
  12. customwas purified by column chromatography (petroleum ether:EtOAc, 6:1 to 5:1)
  13. customto give an impure product
  14. customThe crude material was triturated with a mixture of petroleum ether and EtOAc (3 mL:1 mL)
  15. filtrationthe solid collected by filtration

Sources & evidence

ORD record
ord-e7208544fbde4f24bf1fced50adcd712
Source dataset
uspto-grants-2016_02
Patent number
US09249085B2

Reaction notes

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