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Water → 2-Fluoro-N-(6-fluoro-3-hydroxy-2-methyl-phenyl)-5-(3-fluorophenyl)benzamide

HRID 1771654
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HRID 1771654 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]([CH3:33])=[C:27]([OH:32])[CH:28]=[CH:29][C:30]=1[F:31].O>C(Cl)Cl.CN(C=O)C.C1COCC1>[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]([NH:24][C:25]1[C:30]([F:31])=[CH:29][CH:28]=[C:27]([OH:32])[C:26]=1[CH3:33])=[O:6]
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참가 물질

8

반응물 4

HCID 962WaterHCID 65578Oxalyl chlorideHCID 177757273-Amino-4-fluoro-2-methylphenolHCID 463123323',4-Difluoro-[1,1'-biphenyl]-3-carboxylic acid

생성물 1

HCID 894442512-Fluoro-N-(6-fluoro-3-hydroxy-2-methyl-phenyl)-5-(3-fluorophenyl)benzamide수율 59.1%

시약·촉매·용매 3

HCID 6228
Dimethylformamide
촉매
HCID 6344Dichloromethane용매
HCID 8028Tetrahydrofuran용매2회

실험 절차

To a mixture of 2-fluoro-5-(3-fluorophenyl)benzoic acid (intermediate III(a)) (365 mg, 1.56 mmol, 1.1 eq) and (COCl)2 (541 mg, 4.26 mmol, 3.0 eq) in DCM (10 mL) was added DMF (3 drops). The reaction mixture was stirred at room temperature for 2 h, then concentrated in vacuo. The residue obtained was dissolved in THF (5 mL) and added dropwise to a solution of 3-amino-4-fluoro-2-methyl-phenol (200 mg, 1.42 mmol, 1.0 eq) in THF (15 mL) at 0° C. After the addition was completed, the reaction mixture was allowed to warm to room temperature and stirred for 2 h. The resulting mixture was poured into water and extracted with EtOAc. The organic extract was washed with water and brine, dried (Na2SO4), filtered, evaporated in vacuo and purified by column chromatography (EtOAc:petroleum ether, 0:1 to 1:3) to give the title compound as a yellow solid (300 mg, 59%).

후처리

  1. concentrationconcentrated in vacuo
  2. customThe residue obtained
  3. additionAfter the addition
  4. temperatureto warm to room temperature
  5. stirringstirred for 2 h
  6. extractionextracted with EtOAc
  7. extractionThe organic extract
  8. washwas washed with water and brine
  9. dry with materialdried (Na2SO4)
  10. filtrationfiltered
  11. customevaporated in vacuo
  12. custompurified by column chromatography (EtOAc:petroleum ether, 0:1 to 1:3)

출처 및 근거

ORD 기록
ord-c650287e00a54d5d8a05b6cab90c1bfa
출처 데이터셋
uspto-grants-2016_02
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09249085B2

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