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

HRID 1771606노트

반응식

HRID 1771606 반응식
[F:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:9]=[C:10]([CH:14]=[CH:15][CH:16]=2)[C:11]([OH:13])=O)[CH:5]=[CH:6][CH:7]=1.C(Cl)(C(Cl)=O)=O.[NH2:23][C:24]1[C:25]([F:32])=[C:26]([OH:31])[CH:27]=[CH:28][C:29]=1[F:30].C([O-])(O)=O.[Na+]>C(Cl)Cl.C1COCC1.CN(C=O)C>[F:32][C:25]1[C:26]([OH:31])=[CH:27][CH:28]=[C:29]([F:30])[C:24]=1[NH:23][C:11](=[O:13])[C:10]1[CH:14]=[CH:15][CH:16]=[C:8]([C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[CH:3]=2)[CH:9]=1

참가 물질

8

반응물 4

HCID 65578Oxalyl chlorideHCID 516892Sodium BicarbonateHCID 27826853'-Fluoro[1,1'-biphenyl]-3-carboxylic acidHCID 227559833-Amino-2,4-difluorophenol

생성물 1

HCID 89443548N-(2,6-Difluoro-3-hydroxy-phenyl)-3-(3-fluorophenyl)benzamide수율 50%

시약·촉매·용매 3

HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매HCID 8028Tetrahydrofuran용매

실험 절차

To a stirred solution of 3-(3-fluorophenyl)benzoic acid (430 mg, 1.99 mmol, 1.1 eq), in CH2Cl2 (10 mL) and DMF (0.15 mL) at 0° C. was added (COCl)2 (760 mg, 5.97 mmol, 3.3 eq) dropwise. The reaction was stirred for 2 h, then the solvent removed. The residue dissolved in THF (6 mL) and added to a mixture of 3-amino-2,4-difluoro-phenol (intermediate X(a)) (262.5 mg, 1.81 mmol, 1.0 eq) and NaHCO3 (760 mg, 9.05 mmol, 5 eq) in THF (6 mL) at 0° C. The reaction was stirred for 3 h then quenched by addition of water. The aqueous layer was extracted with EtOAc and the combined organic extracts were washed with Na2CO3, water and brine, dried (Na2SO4), filtered and evaporated in vacuo. The crude residue was crystallised from petroleum ether:EtOAc 3:1 to give the title compound (310 mg, 50%). Evaporation of the filtrate provided a further 180 mg of impure material.

후처리

  1. customthe solvent removed
  2. dissolutionThe residue dissolved in THF (6 mL)
  3. stirringThe reaction was stirred for 3 h
  4. customthen quenched by addition of water
  5. extractionThe aqueous layer was extracted with EtOAc
  6. washthe combined organic extracts were washed with Na2CO3, water and brine
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. customevaporated in vacuo
  10. customThe crude residue was crystallised from petroleum ether:EtOAc 3:1

출처 및 근거

ORD 기록
ord-cb7daa19ad6a4ec6b8d14059f481b9fd
출처 데이터셋
uspto-grants-2016_02
특허 번호
US09249085B2

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