Potassium Iodide → 3'-[(3-Bromopyridin-2-yl)methyl]-2,3-dihydrospiro[furo[2,3-g][1,4]-benzodioxine-8,1'-inden]-2'(3'H)-one

HRID 1965700Notes

Reaction equation

HRID 1965700 reaction equation
[Br:1][C:2]1[C:3]([CH2:8]O)=[N:4][CH:5]=[CH:6][CH:7]=1.S(Cl)(Cl)=O.N1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[C:16]2([C:34]3[C:25](=[CH:26][C:27]4[O:32][CH2:31][CH2:30][O:29][C:28]=4[CH:33]=3)[O:24][CH2:23]2)[C:15]1=[O:35].[C:36](=O)([O-])[O-].[Cs+].[Cs+].[I-].[K+]>ClCCl.CN(C)C=O>[Br:1][C:2]1[C:3]([CH2:8][CH:36]2[C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[C:16]3([C:34]4[C:25](=[CH:26][C:27]5[O:32][CH2:31][CH2:30][O:29][C:28]=5[CH:33]=4)[O:24][CH2:23]3)[C:15]2=[O:35])=[N:4][CH:5]=[CH:6][CH:7]=1

Participants

8

Reactant 5

HCID 4875Potassium IodideHCID 10796Cesium carbonateHCID 24386Thionyl ChlorideHCID 14022521(3-Bromopyridin-2-yl)methanolHCID 58224164Spiro[furo[2,3-g]-1,4-benzodioxin-8(7H),3'-[3H]indol]-2'(1'H)-one, 2,3-dihydro

Product 1

HCID 673576033'-[(3-Bromopyridin-2-yl)methyl]-2,3-dihydrospiro[furo[2,3-g][1,4]-benzodioxine-8,1'-inden]-2'(3'H)-oneYield 59.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent

Procedure

A mixture of (3-bromopyridin-2-yl)methanol (0.100 g, 0.530 mmol) and thionyl chloride (0.070 mL, 0.97 mmol) in dichloromethane (3 mL) and N,N-dimethylformamide (1 drop) was stirred at ambient temperature for 16 h. The reaction mixture was concentrated in vacuo and tetrahydrofuran (5 mL) and N,N-dimethylformamide (5 mL) were added, followed by 2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3′-indol]-2′(1′H)-one (0.121 g, 0.41 mmol), cesium carbonate (0.374 g, 1.15 mmol), and potassium iodide (0.038 g, 0.23 mmol). The mixture was heated at 100° C. for 1 h, allowed to cool to ambient temperature and concentrated in vacuo. The residue was triturated sequentially with water and methanol and further purified by column chromatography and eluted with a 0% to 50% gradient of ethyl acetate in dichloromethane to afford 3′-[(3-bromopyridin-2-yl)methyl]-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,1′-inden]-2′(3′H)-one (0.113 g, 59%) as a colorless solid: mp 217-218° C.; 1H NMR (300 MHz, DMSO-d6) δ 8.41 (d, 1H, J=4.0 Hz), 8.15 (d, J=8.1 Hz, 1H), 7.24 (m, 1H), 6.50 (s, 1H), 6.43 (s, 1H), 5.13 (ABq, 2H), 4.75 (ABq, 2H), 4.14-4.09 (m, 4H); 13C NMR (75 MHz, DMSO-d6) δ 177.3, 155.0, 152.6, 148.3, 144.6, 143.3, 141.3, 138.2, 132.4, 129.1, 125.1, 123.9, 123.3, 122.1, 120.2, 112.3, 109.7, 99.0, 79.7, 64.7, 64.1, 57.7, 44.7; MS (ES+) m/z 464.6 (M+1), 466.6 (M+1).

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo and tetrahydrofuran (5 mL) and N,N-dimethylformamide (5 mL)
  2. additionwere added
  3. temperatureThe mixture was heated at 100° C. for 1 h
  4. temperatureto cool to ambient temperature
  5. concentrationconcentrated in vacuo
  6. customThe residue was triturated sequentially with water and methanol
  7. customfurther purified by column chromatography
  8. washeluted with a 0% to 50% gradient of ethyl acetate in dichloromethane

Sources & evidence

ORD record
ord-818676ab77f044658d9c980e91eae41e
Source dataset
uspto-grants-2013_04
Patent number
US08415370B2

Reaction notes

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