Hydrochloric Acid → 2-Fluoro-N-(6-fluoro-3-hydroxy-2-methyl-phenyl)-5-(3-fluorophenyl)-3-methyl-benzamide

HRID 1771747Notes

Reaction equation

HRID 1771747 reaction equation
[F:1][C:2]1[C:10]([CH3:11])=[CH:9][C:8]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([F:18])[CH:13]=2)=[CH:7][C:3]=1[C:4]([OH:6])=O.C(Cl)(C(Cl)=O)=O.[NH2:25][C:26]1[C:27]([CH3:34])=[C:28]([OH:33])[CH:29]=[CH:30][C:31]=1[F:32].C([O-])(O)=O.[Na+].Cl>C(Cl)Cl.CN(C=O)C.C1COCC1.O>[F:1][C:2]1[C:10]([CH3:11])=[CH:9][C:8]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([F:18])[CH:13]=2)=[CH:7][C:3]=1[C:4]([NH:25][C:26]1[C:31]([F:32])=[CH:30][CH:29]=[C:28]([OH:33])[C:27]=1[CH3:34])=[O:6]

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 65578Oxalyl chlorideHCID 516892Sodium BicarbonateHCID 177757273-Amino-4-fluoro-2-methylphenolHCID 894436582-Fluoro-5-(3-fluorophenyl)-3-methyl-benzoic acid

Product 1

HCID 894452152-Fluoro-N-(6-fluoro-3-hydroxy-2-methyl-phenyl)-5-(3-fluorophenyl)-3-methyl-benzamideYield 53.9%

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 2-fluoro-5-(3-fluorophenyl)-3-methyl-benzoic acid (intermediate III(f)) (528 mg, 2.1 mmol, 1.0 eq), in CH2Cl2 (20 mL) and DMF (3 drops) was added (COCl)2 (0.5 mL). The reaction was stirred at room temperature for 1 h then the solvent and excess reagent were removed under reduced pressure. The residue obtained was dissolved in THF (20 mL) and added to a mixture of 3-amino-4-fluoro-2-methylphenol (intermediate X(e)) (300 mg, 2.1 mmol, 1.0 eq) and NaHCO3 (536 mg, 6.38 mmol, 3 eq) in THF (20 mL) at 0° C. After addition was completed, the reaction mixture was stirred at room temperature for 30 min. Water was added and the aqueous phase was adjusted to pH 3 by addition of diluted HCl. The aqueous solution was extracted with EtOAc and the combined organic extracts were dried (Na2SO4), filtered and evaporated in vacuo. The residue obtained was purified by column chromatography (petroleum ether:EtOAc, 100:1 to 1:1) to give the title compound as a white solid (420 mg, 53%).

Workup

  1. customthe solvent and excess reagent were removed under reduced pressure
  2. customThe residue obtained
  3. additionAfter addition
  4. stirringthe reaction mixture was stirred at room temperature for 30 min
  5. extractionThe aqueous solution was 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, 100:1 to 1:1)

Sources & evidence

ORD record
ord-6dbc15dd2f9649f79adba310cfe35e46
Source dataset
uspto-grants-2016_02
Patent number
US09249085B2

Reaction notes

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