Hydrochloric Acid → 2-fluoro-4-hydroxy-5-[3-hydroxy-1-(4-methoxybenzyl)-2-oxo-2,3-dihydro-1H-indol-3-yl]benzonitrile

HRID 1407494노트

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HRID 1407494 반응식
[F:1][C:2]1[CH:9]=[C:8]([OH:10])[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].C([Mg]Cl)(C)C.[CH3:16][O:17][C:18]1[CH:35]=[CH:34][C:21]([CH2:22][N:23]2[C:31]3[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=3)[C:25](=[O:32])[C:24]2=[O:33])=[CH:20][CH:19]=1.Cl>ClCCCl.O1CCCC1>[F:1][C:2]1[CH:9]=[C:8]([OH:10])[C:7]([C:25]2([OH:32])[C:26]3[C:31](=[CH:30][CH:29]=[CH:28][CH:27]=3)[N:23]([CH2:22][C:21]3[CH:34]=[CH:35][C:18]([O:17][CH3:16])=[CH:19][CH:20]=3)[C:24]2=[O:33])=[CH:6][C:3]=1[C:4]#[N:5]

참가 물질

7

반응물 4

HCID 313Hydrochloric AcidHCID 20487021-(4-methoxybenzyl)-1H-indole-2,3-dioneHCID 27346752-Fluoro-4-hydroxybenzonitrileHCID 178418918HCID 178418918, 화합물

생성물 1

HCID 673583502-fluoro-4-hydroxy-5-[3-hydroxy-1-(4-methoxybenzyl)-2-oxo-2,3-dihydro-1H-indol-3-yl]benzonitrile수율 54.2%

시약·촉매·용매 2

HCID 111,2-Dichloroethane용매HCID 8028Tetrahydrofuran용매

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온도
0 °C

실험 절차

To a stirred solution of 2-fluoro-4-hydroxybenzonitrile (8.00 g, 58.3 mmol) in 1,2-dichloroethane (500 mL) and tetrahydrofuran (50 mL) was added isopropylmagnesium chloride (29.2 mL, 2.0 M solution in tetrahydrofuran, 58.4 mmol) at 0° C. The mixture was stirred at 0° C. for 1 h and at ambient temperature for 2 h. 1-(4-methoxybenzyl)-1H-indole-2,3-dione (15.0 g, 56.1 mmol) was added and the reaction mixture was stirred at reflux for 156 h. The mixture was cooled to 0° C. and 10% w/v hydrochloric acid was added. The phases were separated and the aqueous layer was extracted with dichloromethane (100 mL). The combined organic extracts were washed with water and brine, dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo. The residue was subjected to column chromatography and eluted with ethyl acetate/hexanes (1/1) to afford 2-fluoro-4-hydroxy-5-[3-hydroxy-1-(4-methoxybenzyl)-2-oxo-2,3-dihydro-1H-indol-3-yl]benzonitrile (12.30 g, 54%): 1H NMR (300 MHz, DMSO-d6) δ 8.05 (d, J=9.0 Hz, 1H), 7.34-7.32 (m, 2H), 7.17-7.11 (m, 1H), 6.91-6.76 (m, 7H), 4.78 (ABq, 2H), 3.72 (s, 3H); MS (ES+) m/z 404.9 (M+1).

후처리

  1. stirringthe reaction mixture was stirred
  2. temperatureat reflux for 156 h
  3. temperatureThe mixture was cooled to 0° C.
  4. additionwas added
  5. customThe phases were separated
  6. extractionthe aqueous layer was extracted with dichloromethane (100 mL)
  7. washThe combined organic extracts were washed with water and brine
  8. dry with materialdried over anhydrous sodium sulfate
  9. filtrationfiltered
  10. concentrationThe filtrate was concentrated in vacuo
  11. washeluted with ethyl acetate/hexanes (1/1)

출처 및 근거

ORD 기록
ord-c0d9b04e2d274e54923cf1edcabeada0
출처 데이터셋
uspto-grants-2014_12
특허 번호
US08916580B2

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