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

HRID 1771612노트

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HRID 1771612 반응식
[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]

참가 물질

9

반응물 4

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

생성물 1

HCID 89443896N-(2,6-Difluoro-3-hydroxy-phenyl)-2-fluoro-3-(3-fluorophenyl)-5-methoxy-benzamide수율 55.6%

시약·촉매·용매 4

HCID 6228Dimethylformamide촉매HCID 962Water용매HCID 6344Dichloromethane용매HCID 8028Tetrahydrofuran용매

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온도
0 °C

실험 절차

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%).

후처리

  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)

출처 및 근거

ORD 기록
ord-e819554d1aaf4e3b888388a5f24c2f44
출처 데이터셋
uspto-grants-2016_02
특허 번호
US09249085B2

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