Potassium Carbonate → HCID 89444441, compound

HRID 1771730Notes

Reaction equation

HRID 1771730 reaction equation
[F:1][C:2]1[C:3]([CH3:18])=[C:4]([CH:8]=[C:9]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([F:17])[CH:12]=2)[CH:10]=1)[C:5]([OH:7])=O.C(Cl)(C(Cl)=O)=O.[NH2:25][C:26]1[C:27]([F:34])=[C:28]([OH:33])[CH:29]=[CH:30][C:31]=1[F:32].C([O-])([O-])=O.[K+].[K+]>C(Cl)Cl.C1COCC1.O.CN(C=O)C>[F:34][C:27]1[C:28]([OH:33])=[CH:29][CH:30]=[C:31]([F:32])[C:26]=1[NH:25][C:5](=[O:7])[C:4]1[CH:8]=[C:9]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([F:17])[CH:12]=2)[CH:10]=[C:2]([F:1])[C:3]=1[CH3:18]

Participants

9

Reactant 4

HCID 11430Potassium CarbonateHCID 65578Oxalyl chlorideHCID 227559833-Amino-2,4-difluorophenolHCID 894451373-Fluoro-5-(3-fluorophenyl)-2-methyl-benzoic acid

Product 1

HCID 89444441HCID 89444441, compoundYield 54.5%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 3-fluoro-5-(3-fluorophenyl)-2-methyl-benzoic acid (1.1 g, 4.4 mmol, 1 eq) in CH2Cl2 (15 mL) at 0° C. was added DMF (0.05 mL), and (COCl)2 (1.68 g, 13.2 mmol, 3 eq). The reaction mixture was stirred at room temperature for 3 h. The resulting mixture was concentrated to dryness under reduced pressure and the residue obtained dissolved in THF (10 mL) and added dropwise to a solution of 3-amino-2,4-difluoro-phenol (intermediate X(a)) (770 mg, 5.3 mmol, 1.2 eq) and K2CO3 (3 g, 22.1 mmol, 5 eq) in THF (20 mL) at 0° C. After the addition, the reaction mixture was stirred for 2 h and then water added and the aqueous layer extracted with EtOAc. The combined organic extracts were dried (Na2SO4), filtered and evaporated in vacuo. The residue obtained was purified by column chromatography (petroleum ether:EtOAc, 10:1 to 3:1) to give the title compound as a white solid (0.9 g, 54%).

Workup

  1. concentrationThe resulting mixture was concentrated to dryness under reduced pressure
  2. customthe residue obtained
  3. additionAfter the addition
  4. stirringthe reaction mixture was stirred for 2 h
  5. extractionthe aqueous layer extracted with EtOAc
  6. dry with materialThe combined organic extracts were dried (Na2SO4)
  7. filtrationfiltered
  8. customevaporated in vacuo
  9. customThe residue obtained
  10. customwas purified by column chromatography (petroleum ether:EtOAc, 10:1 to 3:1)

Sources & evidence

ORD record
ord-14761b24d8954a33b8458dd16a077ba7
Source dataset
uspto-grants-2016_02
Patent number
US09249085B2

Reaction notes

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