Potassium Iodide → 1'-{[3-(trifluoromethyl)pyridin-2-yl]methyl}-2,3-dihyrospiro[furo[2,3-f][1,4]benzodioxine-7,3'-indol]-2'(1'H)-one

HRID 2385315Notes

Reaction equation

HRID 2385315 reaction equation
Cl.[F:2][C:3]([F:13])([F:12])[C:4]1[C:5]([CH2:10]O)=[N:6][CH:7]=[CH:8][CH:9]=1.S(Cl)(Cl)=O.[NH:18]1[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[C:20]2([C:30]3[CH:31]=[CH:32][C:33]4[O:34][CH2:35][CH2:36][O:37][C:38]=4[C:29]=3[O:28][CH2:27]2)[C:19]1=[O:39].C(=O)([O-])[O-].[Cs+].[Cs+].[I-].[K+]>ClCCl.CN(C)C=O>[F:2][C:3]([F:13])([F:12])[C:4]1[C:5]([CH2:10][N:18]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[C:20]3([C:30]4[CH:31]=[CH:32][C:33]5[O:34][CH2:35][CH2:36][O:37][C:38]=5[C:29]=4[O:28][CH2:27]3)[C:19]2=[O:39])=[N:6][CH:7]=[CH:8][CH:9]=1

Participants

8

Reactant 5

HCID 4875Potassium IodideHCID 10796Cesium carbonateHCID 24386Thionyl ChlorideHCID 17749867(3-(Trifluoromethyl)pyridin-2-yl)methanol hydrochlorideHCID 593523822,3-dihydrospiro[furo[2,3-f][1,4]benzodioxine-7,3'-indol]-2'(1'H)-one

Product 1

HCID 593521031'-{[3-(trifluoromethyl)pyridin-2-yl]methyl}-2,3-dihyrospiro[furo[2,3-f][1,4]benzodioxine-7,3'-indol]-2'(1'H)-oneYield 27%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of (3-(trifluoromethyl)pyridin-2-yl)methanol hydrochloride (0.324 g, 1.52 mmol) and thionyl chloride (0.174 mL, 2.39 mmol) in anhydrous dichloromethane (10 mL) was stirred at ambient temperature for 16 h. The reaction mixture was concentrated in vacuo and anhydrous N,N-dimethylformamide (10 mL) was added. To this mixture was added 2,3-dihydrospiro[furo[2,3-f][1,4]benzodioxine-7,3′-indol]-2′(1′H)-one (0.300 g, 1.01 mmol), cesium carbonate (0.926 g, 2.84 mmol), potassium iodide (0.094 g, 0.57 mmol) and anhydrous N,N-dimethylformamide (15 mL) and the mixture was heated at 90° C. for 1 h. The reaction mixture was allowed to cool to ambient temperature, concentrated in vacuo, and the resulting residue was taken up in water (50 mL), sonicated and filtered. The solid was purified by column chromatography and eluted with a 0% to 40% gradient of ethyl acetate in dichloromethane followed by recrystallization from methanol to afford 1′-{[3-(trifluoromethyl)pyridin-2-yl]methyl}-2,3-dihyrospiro[furo[2,3-f][1,4]benzodioxine-7,3′-indol]-2′(1′H)-one (0.123 g, 27%) as a colorless solid: mp 206-207° C.; 1H NMR (300 MHz, DMSO-d6) δ 8.72 (d, J=4.4 Hz, 1H), 8.24 (d, J=7.9 Hz, 1H), 7.55 (dd, J=7.8, 5.0 Hz, 1H), 7.26-7.20 (m, 2H), 7.01 (dd, J=11.3, 3.8 Hz, 1H), 6.88 (d, J=7.6 Hz, 1H), 6.36 (s, 2H), 5.22 (ABq, 2H), 4.83 (ABq, 2H), 4.27 (s, 4H); 13C NMR (75 MHz, DMSO-d6) δ 177.0, 152.6, 152.4, 148.7, 144.6, 142.9, 134.9, 131.7, 129.1, 128.6, 123.5, 123.0, 122.8, 122.6, 122.5, 122.0, 114.8, 110.0, 108.9, 80.1, 64.1, 63.9, 57.3, 41.8; MS (ES+) m/z 455.0 (M+1).

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo and anhydrous N,N-dimethylformamide (10 mL)
  2. additionwas added
  3. temperaturethe mixture was heated at 90° C. for 1 h
  4. temperatureto cool to ambient temperature
  5. concentrationconcentrated in vacuo
  6. customsonicated
  7. filtrationfiltered
  8. customThe solid was purified by column chromatography
  9. washeluted with a 0% to 40% gradient of ethyl acetate in dichloromethane
  10. customfollowed by recrystallization from methanol

Sources & evidence

ORD record
ord-53c7e02483e0439684ebac521c9f0033
Source dataset
uspto-grants-2012_09
Patent number
US08263606B2

Reaction notes

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