Sodium hydride → N-(2,6-dichloro-3-methoxy-phenyl)-2-fluoro-5-(3-fluorophenyl) benzamide

HRID 1771680Notes

Reaction equation

HRID 1771680 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.[Cl:18][C:19]1[C:25]([O:26][CH3:27])=[CH:24][CH:23]=[C:22]([Cl:28])[C:20]=1[NH2:21].[H-].[Na+]>O=S(Cl)Cl.C1COCC1>[Cl:18][C:19]1[C:25]([O:26][CH3:27])=[CH:24][CH:23]=[C:22]([Cl:28])[C:20]=1[NH:21][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

6

Reactant 3

HCID 24758Sodium hydrideHCID 205138882,6-Dichloro-3-methoxyanilineHCID 463123323',4-Difluoro-[1,1'-biphenyl]-3-carboxylic acid

Product 1

HCID 89444055N-(2,6-dichloro-3-methoxy-phenyl)-2-fluoro-5-(3-fluorophenyl) benzamideYield 21.3%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 24386Thionyl ChlorideSolvent

Procedure

A solution of 2-fluoro-5-(3-fluorophenyl)benzoic acid (intermediate III(a)) (1.6 g, 7 mmol, 3.0 eq) in SOCl2 (20 mL) was heated at reflux for 3 h. The excess thionyl chloride was removed in vacuo and the residue obtained dissolved in THF (10 mL) and added dropwise to a solution of 2,6-dichloro-3-methoxy-aniline (450 mg, 2.3 mmol, 1.0 eq) and NaH (85 mg, 3.4 mmol, 1.5 eq) in THF (10 mL). The reaction was stirred at room temperature for 2 h then quenched by addition of aqueous NH4Cl. The mixture 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 (EtOAc:petroleum ether, 0:1 to 1:4) to give the title compound (200 mg, 21%).

Workup

  1. temperatureat reflux for 3 h
  2. customThe excess thionyl chloride was removed in vacuo
  3. customthe residue obtained
  4. customthen quenched by addition of aqueous NH4Cl
  5. extractionThe mixture 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 (EtOAc:petroleum ether, 0:1 to 1:4)

Sources & evidence

ORD record
ord-a4c8a2d69f7e452696571e354b03caf9
Source dataset
uspto-grants-2016_02
Patent number
US09249085B2

Reaction notes

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