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

HRID 1771665
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HRID 1771665 반응식
[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.C(Cl)(C(Cl)=O)=O.[NH2:24][C:25]1[C:26]([Cl:33])=[C:27]([OH:32])[CH:28]=[CH:29][C:30]=1[F:31].C([O-])(O)=O.[Na+]>C(Cl)Cl.CN(C=O)C.C1COCC1.O>[Cl:33][C:26]1[C:27]([OH:32])=[CH:28][CH:29]=[C:30]([F:31])[C:25]=1[NH:24][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]
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

9

반응물 4

HCID 65578Oxalyl chlorideHCID 516892Sodium BicarbonateHCID 216600263-Amino-2-chloro-4-fluorophenolHCID 463123323',4-Difluoro-[1,1'-biphenyl]-3-carboxylic acid

생성물 1

HCID 89443695N-(2-chloro-6-fluoro-3-hydroxy-phenyl)-2-fluoro-5-(3-fluorophenyl)benzamide수율 26%

시약·촉매·용매 4

HCID 6228
Dimethylformamide
촉매
HCID 962Water용매
HCID 6344Dichloromethane용매
HCID 8028Tetrahydrofuran용매2회

실험 절차

To a solution of 2-fluoro-5-(3-fluorophenyl)benzoic acid (intermediate III(a)) (478 mg, 2.04 mmol, 1.1 eq) in DCM (9 mL) and DMF (3 drops) at 0° C. was added (COCl)2 (779 mg, 6.14 mmol, 3.3 eq) dropwise. The reaction mixture was stirred at room temperature for 1.5 h, then the solvent removed in vacuo. The residue obtained was dissolved in THF (7 mL) and added dropwise to a mixture of 3-amino-2-chloro-4-fluoro-phenol (intermediate X(f)) (300 mg, 1.86 mmol, 1.0 eq) and NaHCO3 (781 mg, 9.3 mmol, 5.0 eq) in THF (7 mL) at 0° C. After addition was completed, the reaction mixture was warmed to room temperature and stirred overnight. Water was added and the aqueous mixture was extracted with EtOAc. The organic extract was washed with 5% Na2CO3, water and brine, dried (Na2SO4), filtered, evaporated in vacuo and purified by column chromatography (EtOAc:petroleum ether, 3:20 to 1:4) to give the title as a yellow solid compound (180 mg, 26%).

후처리

  1. customthe solvent removed in vacuo
  2. customThe residue obtained
  3. additionAfter addition
  4. temperaturethe reaction mixture was warmed to room temperature
  5. stirringstirred overnight
  6. extractionthe aqueous mixture was extracted with EtOAc
  7. extractionThe organic extract
  8. washwas washed with 5% Na2CO3, water and brine
  9. dry with materialdried (Na2SO4)
  10. filtrationfiltered
  11. customevaporated in vacuo
  12. custompurified by column chromatography (EtOAc:petroleum ether, 3:20 to 1:4)

출처 및 근거

ORD 기록
ord-d1d783cf3af84ec08b621292584869a7
출처 데이터셋
uspto-grants-2016_02
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09249085B2

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