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

HRID 1771618노트

반응식

HRID 1771618 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]([CH3:18])=[CH:7][C:3]=1[C:4]([OH:6])=O.C(Cl)(=O)C(Cl)=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.O>[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]([CH3:18])[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 894435072-Fluoro-3-(3-fluorophenyl)-5-methyl-benzoic acid

생성물 1

HCID 89444178N-(2,6-Difluoro-3-hydroxy-phenyl)-2-fluoro-3-(3-fluorophenyl)-5-methyl-benzamide수율 24%

시약·촉매·용매 4

HCID 6228Dimethylformamide촉매HCID 962Water용매HCID 6344Dichloromethane용매HCID 8028Tetrahydrofuran용매

실험 절차

To a stirred solution of 2-fluoro-3-(3-fluorophenyl)-5-methyl-benzoic acid (400 mg, 1.65 mmol, 1.1 eq) in CH2Cl2 (10 mL) was added oxalylchloride (0.5 mL, 5.9 mmol, 4.0 eq) and DMF (2 drops). The reaction was stirred for 1 h, then the solvent removed in vacuo and the residue dissolved in THF (10 mL). The solution was then added dropwise to a mixture of 3-amino-2,4-difluoro-phenol (intermediate X(a)) (212 mg. 1.50 mmol, 1.0 eq) and NaHCO3 (492 mg, 5.90 mmol, 4.0 eq) in THF (10 mL) at room temperature. The reaction was stirred overnight then poured into water and extracted with EtOAc. The combined organic extracts were washed with water and brine, dried (Na2SO4), filtered and evaporated in vacuo. The residue was purified by chromatography (EtOAc:petroleum ether, 0:1 to 1:3) to give the title compound as a solid (130 mg, 24%).

후처리

  1. customthe solvent removed in vacuo
  2. dissolutionthe residue dissolved in THF (10 mL)
  3. stirringThe reaction was stirred overnight
  4. extractionextracted with EtOAc
  5. washThe combined organic extracts were washed with water and brine
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. customevaporated in vacuo
  9. customThe residue was purified by chromatography (EtOAc:petroleum ether, 0:1 to 1:3)

출처 및 근거

ORD 기록
ord-f35a9636a9b9466c9a16b4bc199379d4
출처 데이터셋
uspto-grants-2016_02
특허 번호
US09249085B2

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