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

HRID 1771800노트

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HRID 1771800 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)(C(Cl)=O)=O.[NH2:25][C:26]1[C:27]([CH3:34])=[C:28]([OH:33])[CH:29]=[CH:30][C:31]=1[CH3:32].C([O-])(O)=O.[Na+]>C(Cl)Cl.CN(C=O)C.C1COCC1.O>[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]([NH:25][C:26]1[C:31]([CH3:32])=[CH:30][CH:29]=[C:28]([OH:33])[C:27]=1[CH3:34])=[O:6]

참가 물질

9

반응물 4

HCID 65578Oxalyl chlorideHCID 516892Sodium BicarbonateHCID 141306083-Amino-2,4-dimethylphenolHCID 894435072-Fluoro-3-(3-fluorophenyl)-5-methyl-benzoic acid

생성물 1

HCID 894438592-Fluoro-3-(3-fluorophenyl)-N-(3-hydroxy-2,6-dimethyl-phenyl)-5-methyl-benzamide수율 73%

시약·촉매·용매 4

HCID 6228Dimethylformamide촉매HCID 962Water용매HCID 6344Dichloromethane용매HCID 8028Tetrahydrofuran용매2회

실험 절차

To a solution of 2-fluoro-3-(3-fluorophenyl)-5-methyl-benzoic acid (intermediate III(e)) (597 mg, 2.4 mmol, 1.1 eq) in CH2Cl2 (15 mL) was added (COCl)2 (916 mg, 7.2 mmol, 3.3 eq) and DMF (5 drops). The reaction mixture was stirred at room temperature for 2 h, then the solvent and excess reagent were removed under reduced pressure. The residue obtained was dissolved in THF (20 mL) and added dropwise to a mixture of 3-amino-2,4-dimethylphenol (intermediate X(c)) (300 mg, 2.2 mmol, 1.0 eq) and NaHCO3 (920 mg, 10.9 mmol, 5.0 eq) in THF (20 mL) at 0° C. After the addition was completed, the reaction was allowed to warm to room temperature and stirred for a further 1 h. The reaction was then poured into water and extracted with EtOAc. The combined organic layers were washed with water and brine, dried (Na2SO4), filtered, and evaporated in vacuo. The residue obtained was purified by column chromatography (CH2Cl2:MeOH, 500:1 to 300:1) to give the title compound as a white solid (588 mg, 73%).

후처리

  1. customthe solvent and excess reagent were removed under reduced pressure
  2. customThe residue obtained
  3. additionAfter the addition
  4. temperatureto warm to room temperature
  5. stirringstirred for a further 1 h
  6. extractionextracted with EtOAc
  7. washThe combined organic layers were washed with water and brine
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. customevaporated in vacuo
  11. customThe residue obtained
  12. customwas purified by column chromatography (CH2Cl2:MeOH, 500:1 to 300:1)

출처 및 근거

ORD 기록
ord-ee0a96283b1649d1868bea47dbd72221
출처 데이터셋
uspto-grants-2016_02
특허 번호
US09249085B2

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