Dichloromethane → 1-(diphenylmethyl)-7-fluoro-3-hydroxy-3-(7-hydroxy-2,3-dihydro-1,4-benzodioxin-6-yl)-1,3-dihydro-2H-indol-2-one

HRID 1407480ノート

反応式

HRID 1407480 の反応式
[O:1]1[C:6]2[CH:7]=[CH:8][C:9]([OH:11])=[CH:10][C:5]=2[O:4][CH2:3][CH2:2]1.C([Mg]Cl)(C)C.[F:17][C:18]1[CH:19]=[CH:20][CH:21]=[C:22]2[C:26]=1[N:25]([CH:27]([C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[C:24](=[O:40])[C:23]2=[O:41].ClCCl>O1CCCC1>[C:34]1([CH:27]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[N:25]2[C:26]3[C:22](=[CH:21][CH:20]=[CH:19][C:18]=3[F:17])[C:23]([OH:41])([C:8]3[C:9]([OH:11])=[CH:10][C:5]4[O:4][CH2:3][CH2:2][O:1][C:6]=4[CH:7]=3)[C:24]2=[O:40])[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=1

参加物

6

反応物 4

HCID 6344DichloromethaneHCID 91152732,3-Dihydro-1,4-benzodioxin-6-olHCID 673566781-(diphenylmethyl)-7-fluoro-1H-indole-2,3-dioneHCID 178418918HCID 178418918、化合物

生成物 1

HCID 685991191-(diphenylmethyl)-7-fluoro-3-hydroxy-3-(7-hydroxy-2,3-dihydro-1,4-benzodioxin-6-yl)-1,3-dihydro-2H-indol-2-one収率 84.1%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
0 °C

実験手順

To a cooled (0° C.) suspension of 2,3-dihydro-1,4-benzodioxin-6-ol (0.47 g, 3.0 mmol) in anhydrous tetrahydrofuran (12 mL) was added isopropylmagnesium chloride (2 M solution in tetrahydrofuran, 1.7 mL, 3.3 mmol). The reaction mixture was stirred at 0° C. for 1 h, and 7-fluoro-1-(diphenylmethyl)-1H-indole-2,3-dione (1.0 g, 3.0 mmol) and anhydrous dichloromethane (10 mL) were added. The reaction mixture was allowed to stir for 19 h at ambient temperature. The reaction mixture was concentrated in vacuo and was diluted with saturated aqueous ammonium chloride (30 mL) and ethyl acetate (30 mL). The phases were separated and the aqueous phase was extracted with ethyl acetate (2×50 mL). The combined organic extracts were washed with brine (100 mL), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by column chromatography and eluted with a 8% to 66% gradient of ethyl acetate in hexanes to afford 1-(diphenylmethyl)-7-fluoro-3-hydroxy-3-(7-hydroxy-2,3-dihydro-1,4-benzodioxin-6-yl)-1,3-dihydro-2H-indol-2-one (1.22 g, 84%) as an off-white solid: MS (ES+) m/z 475.0 (M−17).

後処理

  1. temperatureTo a cooled
  2. stirringto stir for 19 h at ambient temperature
  3. concentrationThe reaction mixture was concentrated in vacuo
  4. additionwas diluted with saturated aqueous ammonium chloride (30 mL) and ethyl acetate (30 mL)
  5. customThe phases were separated
  6. extractionthe aqueous phase was extracted with ethyl acetate (2×50 mL)
  7. washThe combined organic extracts were washed with brine (100 mL)
  8. dry with materialdried over anhydrous sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe crude product was purified by column chromatography
  12. washeluted with a 8% to 66% gradient of ethyl acetate in hexanes

出典と根拠

ORDレコード
ord-5d46a4cd13dd4ec2b0a2bbe6f28998f2
出典データセット
uspto-grants-2014_12
特許番号
US08916580B2

反応ノート

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