Hydrochloric Acid → HCID 89443857, compound

HRID 1771646Notes

Reaction equation

HRID 1771646 reaction equation
[Cl: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)(=O)C(Cl)=O.[NH2:24][C:25]1[C:26]([F:33])=[C:27]([OH:32])[CH:28]=[CH:29][C:30]=1[F:31].C([O-])(O)=O.[Na+].Cl>C(Cl)Cl.C1COCC1.CN(C=O)C>[Cl: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:30]([F:31])=[CH:29][CH:28]=[C:27]([OH:32])[C:26]=1[F:33])=[O:6]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 65578Oxalyl chlorideHCID 516892Sodium BicarbonateHCID 227559833-Amino-2,4-difluorophenolHCID 463144754-Chloro-3'-fluoro-[1,1'-biphenyl]-3-carboxylic acid

Product 1

HCID 89443857HCID 89443857, compoundYield 27%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-chloro-5-(3-fluorophenyl)benzoic acid (500 mg, 2.0 mmol, 1.0 eq) in DCM (20 mL) was added oxalyl chloride (761.6 mg, 6.0 mmol, 3.0 eq) and DMF (0.1 mL). The solution was stirred at room temperature for 1 h, then the solvent removed in vacuo. The resultant residue was dissolved in dry THF (30 mL) and added dropwise to a suspension of 3-amino-2,4-difluorophenol (intermediate X(a)) (290.2 mg, 2.0 mmol, 1.0 eq) and NaHCO3 (504 mg, 6.0 mmol, 3.0 eq) in THF (30 mL). The mixture was warmed to room temperature and stirred for 30 min. The pH of the reaction was adjusted to pH 3 by addition of 1M HCl and the aqueous layer was extracted with EtOAc. The combined organic extracts were washed with brine, dried (Na2SO4) filtered and evaporated in vacuo. The residue was purified by chromatography to give the title compound as a white solid (200 mg, 27%).

Workup

  1. customthe solvent removed in vacuo
  2. dissolutionThe resultant residue was dissolved in dry THF (30 mL)
  3. temperatureThe mixture was warmed to room temperature
  4. stirringstirred for 30 min
  5. extractionthe aqueous layer was extracted with EtOAc
  6. washThe combined organic extracts were washed with brine
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. customevaporated in vacuo
  10. customThe residue was purified by chromatography

Sources & evidence

ORD record
ord-e9710f9e77594f25858b1ac5fc787916
Source dataset
uspto-grants-2016_02
Patent number
US09249085B2

Reaction notes

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