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 2385354노트

반응식

HRID 2385354 반응식
[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

참가 물질

7

반응물 4

HCID 4875Potassium IodideHCID 10796Cesium carbonate2회HCID 567764533-(Chloromethyl)-5-fluoropyridine hydrochloride2회HCID 59352191Spiro[furo[2,3-g]-1,4-benzodioxin-8(7H),3'-[3H]indol]-2'(1'H)-one, 2,3-dihydro-, (3'S)-

생성물 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)-one수율 19%

시약·촉매·용매 2

HCID 67553Tetrabutylammonium Iodide촉매HCID 6569Methyl Ethyl Ketone용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-041f683e35494fe8b4d30493e751af92
출처 데이터셋
uspto-grants-2012_09
특허 번호
US08263606B2

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