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

HRID 1771623노트

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HRID 1771623 반응식
[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]([F:34])=[C:28]([OH:33])[CH:29]=[CH:30][C:31]=1[F:32].C([O-])(O)=O.[Na+]>C(Cl)Cl.CN(C=O)C.C1COCC1>[F:34][C:27]1[C:28]([OH:33])=[CH:29][CH:30]=[C:31]([F:32])[C:26]=1[NH:25][C:4](=[O:6])[C:3]1[CH:7]=[C:8]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([F:18])[CH:13]=2)[CH:9]=[C:10]([CH3:11])[C:2]=1[F:1]

참가 물질

8

반응물 4

HCID 65578Oxalyl chlorideHCID 516892Sodium BicarbonateHCID 227559833-Amino-2,4-difluorophenolHCID 894436582-Fluoro-5-(3-fluorophenyl)-3-methyl-benzoic acid

생성물 1

HCID 89443818N-(2,6-difluoro-3-hydroxy-phenyl)-2-fluoro-5-(3-fluorophenyl)-3-methyl-benzamide수율 43%

시약·촉매·용매 3

HCID 6228Dimethylformamide촉매HCID 6344Dichloromethane용매HCID 8028Tetrahydrofuran용매

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온도
0 °C

실험 절차

To a solution of 2-fluoro-5-(3-fluorophenyl)-3-methyl-benzoic acid (558 mg, 2.25 mmol, 1.0 eq) in DCM (30 mL) at 0° C. was added (COCl)2 (856 mg, 0.57 mL, 6.74 mmol, 3 eq) and DMF (2 drops). The reaction was stirred at 0° C. for 2 h then the solvent was removed in vacuo. The residue was taken up in THF (30 mL) and added to a suspension of 3-amino-2,4-difluorophenol (intermediate X(a)) (330 mg, 2.36 mmol, 1.05 eq) and NaHCO3 (566 mg, 6.74 mmol, 3.0 eq) in THF (30 mL) at 0° C. The reaction was stirred for 3 h at 0° C. then quenched by addition of 1 M HCl and the aqueous layer extracted with EtOAc. The combined organic extracts were washed with brine, dried (Na2SO4), filtered and evaporated in vacuo. The crude residue was purified by chromatography (MeOH:DCM, 0:1 to 1:50) to give the title compound as a solid (360 mg, 43%).

후처리

  1. customthe solvent was removed in vacuo
  2. stirringThe reaction was stirred for 3 h at 0° C.
  3. customthen quenched by addition of 1 M HCl
  4. extractionthe aqueous layer extracted with EtOAc
  5. washThe combined organic extracts were washed with brine
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. customevaporated in vacuo
  9. customThe crude residue was purified by chromatography (MeOH:DCM, 0:1 to 1:50)

출처 및 근거

ORD 기록
ord-b861d4f0018c4ca3b37017430057adc5
출처 데이터셋
uspto-grants-2016_02
특허 번호
US09249085B2

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