Acetic Acid → 1-(diphenylmethyl)-3-(4-fluoro-2-hydroxy-5-methoxyphenyl)-1,3-dihydro-2H-indol-2-one

HRID 1965328노트

반응식

HRID 1965328 반응식
[C:1]1([CH:7]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:10]([C:18]3[CH:23]=[C:22]([O:24][CH3:25])[C:21]([F:26])=[CH:20][C:19]=3[OH:27])(O)[C:9]2=[O:28])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(N(CC)CC)C.S(Cl)(Cl)=O.C(O)(=O)C>ClC(Cl)C.[Zn]>[C:29]1([CH:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[CH:10]([C:18]3[CH:23]=[C:22]([O:24][CH3:25])[C:21]([F:26])=[CH:20][C:19]=3[OH:27])[C:9]2=[O:28])[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1

참가 물질

7

반응물 4

HCID 176Acetic AcidHCID 8471TriethylamineHCID 24386Thionyl ChlorideHCID 67357402HCID 67357402, 화합물

생성물 1

HCID 673773961-(diphenylmethyl)-3-(4-fluoro-2-hydroxy-5-methoxyphenyl)-1,3-dihydro-2H-indol-2-one수율 17.3%

시약·촉매·용매 2

HCID 23994Zinc촉매HCID 63651,1-Dichloroethane용매

실험 절차

To a solution of 1-(diphenylmethyl)-3-(4-fluoro-2-hydroxy-5-methoxyphenyl)-3-hydroxy-1,3-dihydro-2H-indol-2-one (6.60 g, 14.5 mmol) in dichloroethane (100 mL) were added triethylamine (4.55 g, 45.0 mmol) and thionyl chloride (3.57 g, 30.0 mmol) at 0° C. The reaction mixture was heated at reflux for 1 h. The reaction mixture was cooled down to ambient temperature and concentrated under reduced pressure. The residue was dissolved in tetrahydrofuran (100 mL) and acetic acid (10 mL) and zinc dust (6.54 g, 100.0 mmol) were added in small portions at ambient temperature. The reaction mixture was stirred at ambient temperature for 16 h and filtered. The filtrate was concentrated in vacuo to dryness. The residue was purified by column chromatography with a 20% to 80% gradient of ethyl acetate in hexanes to afford 1-(diphenylmethyl)-3-(4-fluoro-2-hydroxy-5-methoxyphenyl)-1,3-dihydro-2H-indol-2-one (1.10 g, 17%) as a colorless solid: MS (ES+) m/z 440.2 (M+1).

후처리

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 1 h
  3. concentrationconcentrated under reduced pressure
  4. dissolutionThe residue was dissolved in tetrahydrofuran (100 mL)
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated in vacuo to dryness
  7. customThe residue was purified by column chromatography with a 20% to 80% gradient of ethyl acetate in hexanes

출처 및 근거

ORD 기록
ord-ae18e81b4c0743d2b17bd7010050e74f
출처 데이터셋
uspto-grants-2013_04
특허 번호
US08415370B2

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