Potassium Iodide → (8S)-1'-[(5-fluoropyridin-3-yl)methyl]-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3'-indol]-2'(1'H)-one

HRID 2385354ノート

反応式

HRID 2385354 の反応式
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C@@:3]2([C:21]3[C:12](=[CH:13][C:14]4[O:19][CH2:18][CH2:17][O:16][C:15]=4[CH:20]=3)[O:11][CH2:10]2)[C:2]1=[O:22].C(=O)([O-])[O-].[Cs+].[Cs+].Cl.Cl[CH2:31][C:32]1[CH:33]=[N:34][CH:35]=[C:36]([F:38])[CH:37]=1.[I-].[K+]>CC(=O)CC.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[F:38][C:36]1[CH:37]=[C:32]([CH2:31][N:1]2[C:9]3[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=3)[C@@:3]3([C:21]4[C:12](=[CH:13][C:14]5[O:19][CH2:18][CH2:17][O:16][C:15]=5[CH:20]=4)[O:11][CH2:10]3)[C:2]2=[O:22])[CH:33]=[N:34][CH:35]=1

参加物

7

反応物 4

HCID 4875Potassium IodideHCID 10796Cesium carbonate2 回HCID 567764533-(Chloromethyl)-5-fluoropyridine hydrochloride2 回HCID 59352191Spiro[furo[2,3-g]-1,4-benzodioxin-8(7H),3'-[3H]indol]-2'(1'H)-one, 2,3-dihydro-, (3'S)-

生成物 1

HCID 59352528(8S)-1'-[(5-fluoropyridin-3-yl)methyl]-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3'-indol]-2'(1'H)-one収率 19%

試薬・触媒・溶媒 2

HCID 67553Tetrabutylammonium Iodide触媒HCID 6569Methyl Ethyl Ketone溶媒

実験手順

To a solution of (8S)-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3′-indol]-2′(1′H)-one (0.40 g, 1.35 mmol) in 2-butanone (15 mL) was added cesium carbonate (1.76 g, 5.40 mmol), 3-(chloromethyl)-5-fluoropyridine hydrochloride (0.49 g, 2.69 mmol) and potassium iodide (0.085 g, 38 mol %). This mixture was stirred under nitrogen at ambient temperature for 72 h. Further, cesium carbonate (1.76 g, 5.40 mmol), 3-(chloromethyl)-5-fluoropyridine hydrochloride (0.49 g, 2.69 mmol) and tetra-n-butylammonium iodide (0.08 g, 0.22 mmol) were added and the reaction mixture was heated at reflux for 48 h, allowed to cool to ambient temperature, filtered and concentrated in vacuo. The residue was purified by column chromatography and eluted with a 10% to 40% gradient of ethyl acetate in hexanes and recrystallized from diethyl ether to afford (8S)-1′-[(5-fluoropyridin-3-yl)methyl]-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3′-indol]-2′(1′H)-one (102.1 mg, 19%) as a yellow solid: mp 197-200° C. (diethyl ether); 1H NMR (300 MHz, CDCl3) δ 8.48-8.42 (m, 2H), 7.40-7.37 (m, 1H), 7.26-7.17 (m, 2H), 7.08-7.03 (m, 1H), 6.78-6.76 (m, 1H), 6.50 (s, 1H), 6.18 (s, 1H), 5.06-4.88 (m, 3H), 4.66-4.63 (m, 1H), 4.20-4.09 (m, 4H); 13C NMR (75 MHz, CDCl3) δ 177.7, 155.3, 144.8, 144.4, 141.3, 138.4, 138.0, 137.7, 132.1, 129.0, 124.3, 124.0, 122.4, 122.2, 120.5, 111.4, 108.7, 99.5, 80.1, 64.5, 63.9, 58.0, 41.1; MS (ES+) m/z 404.9 (M+1).

後処理

  1. temperaturethe reaction mixture was heated
  2. temperatureat reflux for 48 h
  3. temperatureto cool to ambient temperature
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by column chromatography
  7. washeluted with a 10% to 40% gradient of ethyl acetate in hexanes
  8. customrecrystallized from diethyl ether

出典と根拠

ORDレコード
ord-041f683e35494fe8b4d30493e751af92
出典データセット
uspto-grants-2012_09
特許番号
US08263606B2

反応ノート

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