Oxalyl chloride → N-(2,6-Difluoro-3-hydroxy-phenyl)-2-fluoro-3-(3-fluorophenyl)-5-methoxy-benzamide

HRID 1771612Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1771612
[F:1][C:2]1[C:10]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([F:17])[CH:12]=2)=[CH:9][C:8]([O:18][CH3:19])=[CH:7][C:3]=1[C:4]([OH:6])=O.C(Cl)(=O)C(Cl)=O.[NH2:26][C:27]1[C:28]([F:35])=[C:29]([OH:34])[CH:30]=[CH:31][C:32]=1[F:33].C([O-])(O)=O.[Na+]>C(Cl)Cl.CN(C=O)C.C1COCC1.O>[F:35][C:28]1[C:29]([OH:34])=[CH:30][CH:31]=[C:32]([F:33])[C:27]=1[NH:26][C:4](=[O:6])[C:3]1[CH:7]=[C:8]([O:18][CH3:19])[CH:9]=[C:10]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([F:17])[CH:12]=2)[C:2]=1[F:1]

Komponenten

9

Edukt 4

HCID 65578Oxalyl chlorideHCID 516892Sodium BicarbonateHCID 227559833-Amino-2,4-difluorophenolHCID 894438332-Fluoro-3-(3-fluorophenyl)-5-methoxybenzoic acid

Produkt 1

HCID 89443896N-(2,6-Difluoro-3-hydroxy-phenyl)-2-fluoro-3-(3-fluorophenyl)-5-methoxy-benzamideAusbeute 55,6 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 6228DimethylformamideKatalysatorHCID 962WaterLösungsmittelHCID 6344DichloromethaneLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

To a solution of 2-fluoro-3-(3-fluorophenyl)-5-methoxybenzoic acid (402 mg, 1.52 mmol, 1.1 eq) in CH2Cl2 (20 mL) at 0° C. was added oxalylchloride (525 mg, 4.14 mmol, 3.0 eq) and DMF (5 drops). The solution was stirred at 0° C. for 2 h then the solvent removed in vacuo. The residue was taken up in THF (10 mL) and added dropwise to a mixture of 3-amino-2,4-difluorophenol (intermediate X(a)) (200 mg, 1.38 mmol, 1.0 eq) and NaHCO3 (348 mg, 4.14 mmol, 3.0 eq) in THF (10 mL) at 0° C. The mixture was stirred at 0° C. for 4 h then poured into water and extracted with EtOAc. The organic extract was washed with water, brine, dried (Na2SO4) filtered and evaporated in vacuo. The residue was purified by column chromatography (EtOAc:petroleum ether, 0:1 to 1:3) to give the title compound as a white solid (300 mg, 50%).

Aufarbeitung

  1. customthe solvent removed in vacuo
  2. stirringThe mixture was stirred at 0° C. for 4 h
  3. extractionextracted with EtOAc
  4. extractionThe organic extract
  5. washwas washed with water, brine
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. customevaporated in vacuo
  9. customThe residue was purified by column chromatography (EtOAc:petroleum ether, 0:1 to 1:3)

Quellen und Nachweise

ORD-Eintrag
ord-e819554d1aaf4e3b888388a5f24c2f44
Quelldatensatz
uspto-grants-2016_02
Patentnummer
US09249085B2

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