Water → HCID 89444094, compound

HRID 1771737Notes

Reaction equation

HRID 1771737 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.O=S(Cl)Cl.[NH2:22][C:23]1[C:24]([F:32])=[C:25]([OH:31])[CH:26]=[C:27]([CH3:30])[C:28]=1[F:29].O>C(Cl)Cl.CN(C=O)C.C1COCC1>[F:32][C:24]1[C:25]([OH:31])=[CH:26][C:27]([CH3:30])=[C:28]([F:29])[C:23]=1[NH:22][C:4](=[O:6])[C:3]1[CH:7]=[C:8]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([F:17])[CH:12]=2)[CH:9]=[CH:10][C:2]=1[F:1]

Participants

8

Reactant 4

HCID 962WaterHCID 24386Thionyl ChlorideHCID 463123323',4-Difluoro-[1,1'-biphenyl]-3-carboxylic acidHCID 894437823-Amino-2,4-difluoro-5-methylphenol

Product 1

HCID 89444094HCID 89444094, compoundYield 45%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 2-fluoro-5-(3-fluorophenyl)benzoic acid (Intermediate III(a)) (437 mg, 1.87 mmol, 1.1 eq) in CH2Cl2 (10 mL) and DMF (3 drops) was added SOCl2 (15 mL) dropwise at 0° C. The solution was stirred at room temperature for 1 h, then concentrated in vacuo. The residue obtained was dissolved in THF (20 mL) and added dropwise to a solution of 3-amino-2,4-difluoro-5-methyl-phenol (270 mg, 1.70 mmol, 1.0 eq) in THF (10 mL) at 0° C. After addition was completed, the reaction mixture was stirred at room temperature for 2 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 (petroleum ether: EtOAc, 10:1 to 3:1) to give the title compound as a white solid (285 mg, 45%).

Workup

  1. concentrationconcentrated in vacuo
  2. customThe residue obtained
  3. additionAfter addition
  4. stirringthe reaction mixture was stirred at room temperature for 2 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 (petroleum ether: EtOAc, 10:1 to 3:1)

Sources & evidence

ORD record
ord-552f183a47ca4dfa8a57912769315f05
Source dataset
uspto-grants-2016_02
Patent number
US09249085B2

Reaction notes

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