3,4-Difluorophenol → 3-(4,5-difluoro-2-hydroxyphenyl)-1-(diphenylmethyl)-3-hydroxy-1,3-dihydro-2H-indol-2-one

HRID 1407458

反応式

HRID 1407458 の反応式
[F:1][C:2]1[CH:3]=[C:4]([OH:9])[CH:5]=[CH:6][C:7]=1[F:8].C([Mg]Cl)(C)C.[CH:15]([N:28]1[C:38]2[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=2)[C:31](=[O:32])[C:29]1=[O:30])([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>O1CCCC1>[F:1][C:2]1[C:7]([F:8])=[CH:6][C:5]([C:31]2([OH:32])[C:33]3[C:38](=[CH:37][CH:36]=[CH:35][CH:34]=3)[N:28]([CH:15]([C:16]3[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=3)[C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[C:29]2=[O:30])=[C:4]([OH:9])[CH:3]=1

参加物

5

反応物 3

HCID 759273,4-DifluorophenolHCID 19692771-(diphenylmethyl)-1H-indole-2,3-dioneHCID 178418918HCID 178418918、化合物

生成物 1

HCID 673574293-(4,5-difluoro-2-hydroxyphenyl)-1-(diphenylmethyl)-3-hydroxy-1,3-dihydro-2H-indol-2-one収率 62.1%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

To a solution of 3,4-difluorophenol (10.33 g, 79.4 mmol) in anhydrous tetrahydrofuran (60 mL) at 0° C. under nitrogen was added isopropyl magnesium chloride (39.7 mL, 79.4 mmol), and the solution was stirred at ambient temperature for 3 h. Tetrahydrofuran was removed by rotary evaporation, and the residue was redissolved in anhydrous dichloromethane (140 mL). The solution was cooled to 0° C. under nitrogen, then N-benzhydryl isatin (13.77 g, 43.9 mmol) was added and the reaction mixture was allowed to warm to ambient temperature. After 3 days, the reaction was quenched with aqueous saturated ammonium chloride (60 mL) and concentrated in vacuo. The residue was re-dissolved in ethyl acetate (150 mL) and washed with water (2×100 mL) and brine (100 mL), dried over sodium sulfate, filtered, and concentrated. The residue was precipitated from diethyl ether to yield 3-(4,5-difluoro-2-hydroxyphenyl)-1-(diphenylmethyl)-3-hydroxy-1,3-dihydro-2H-indol-2-one (12.08 g, 61%) as a colorless solid: 1H NMR (300 MHz, CDCl3) δ 9.23 (br s, 1H), 7.47-7.44 (m, 1H), 7.35-7.21 (m, 9H), 7.18-7.11 (m, 2H), 6.90 (s, 1H), 6.83 (dd, J=11.2, 6.9 Hz, 1H), 6.67 (dd, J=11.2, 8.7 Hz, 1H), 6.56-6.51 (m, 1H), 4.13 (br s, 1H); MS (ES+) m/z 426.2 (M−17).

後処理

  1. customTetrahydrofuran was removed by rotary evaporation
  2. dissolutionthe residue was redissolved in anhydrous dichloromethane (140 mL)
  3. temperatureThe solution was cooled to 0° C. under nitrogen
  4. temperatureto warm to ambient temperature
  5. waitAfter 3 days
  6. customthe reaction was quenched with aqueous saturated ammonium chloride (60 mL)
  7. concentrationconcentrated in vacuo
  8. dissolutionThe residue was re-dissolved in ethyl acetate (150 mL)
  9. washwashed with water (2×100 mL) and brine (100 mL)
  10. dry with materialdried over sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customThe residue was precipitated from diethyl ether

出典と根拠

ORDレコード
ord-f2a7e4cb1ade42aeb3b8bebf16c19d7b
出典データセット
uspto-grants-2014_12
特許番号
US08916580B2

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