Sodium hydride → HCID 46195987, compound

HRID 1965620Notes

Reaction equation

HRID 1965620 reaction equation
[CH3:1][C:2]1[C:6]2[CH:7]=[C:8]3[C:13]4([C:21]5[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=5)[NH:15][C:14]4=[O:22])[CH2:12][O:11][C:9]3=[CH:10][C:5]=2[O:4][N:3]=1.[H-].[Na+].Br[CH2:26][C:27]1[O:28][C:29]([C:32]([F:35])([F:34])[F:33])=[CH:30][CH:31]=1>CN(C)C=O.C(OCC)(=O)C>[CH3:1][C:2]1[C:6]2[CH:7]=[C:8]3[C:13]4([C:21]5[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=5)[N:15]([CH2:26][C:27]5[O:28][C:29]([C:32]([F:35])([F:34])[F:33])=[CH:30][CH:31]=5)[C:14]4=[O:22])[CH2:12][O:11][C:9]3=[CH:10][C:5]=2[O:4][N:3]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 27946052-(Bromomethyl)-5-(trifluoromethyl)furanHCID 593524533-methylspiro[furo[3,2-f][1,2]benzisoxazole-5,3'-indol]-2'(1H)-one

Product 1

HCID 46195987HCID 46195987, compoundYield 80%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of 3-methylspiro[furo[3,2-f][1,2]benzisoxazole-5,3′-indol]-2′(1′H)-one (0.29 g, 1.00 mmol) in N,N-dimethylformamide (10 mL) was added sodium hydride (0.05 g, 1.25 mmol) at 0° C. The reaction mixture was stirred at 0° C. for 30 min, then 2-(bromomethyl)-5-(trifluoromethyl)furan (0.25 mL, 1.80 mmol) was added. The mixture was stirred at ambient temperature for 20 h, diluted with ethyl acetate, washed with water and brine, and dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuum. The residue was purified by column chromatography with ethyl acetate in hexanes (10% to 40% gradient) to afford 3-methyl-1′-{[5-(trifluoromethyl)furan-2-yl]methyl}spiro[furo[3,2-f][1,2]benzisoxazole-5,3′-indol]-2′(1′H)-one (0.35 g, 80%): mp 111-112° C. (diethyl ether/hexanes); 1H NMR (300 MHz, CDCl3) δ7.46 (d, J=9.0 Hz, 1H), 7.33-7.27 (m, 1H), 7.15-7.12 (m, 1 H), 7.06-7.01 (m, 3H), 6.77-6.76 (m, 1H), 6.55-6.52 (m, 1H), 5.20-4.85 (m, 4H), 2.44 (s, 3H); 13C NMR (75 MHz, CDCl3) δ175.7, 163.9, 158.1, 154.9, 151.6, 141.4, 130.2, 129.5, 123.9, 123.1, 120.7, 117.9, 117.1, 112.9, 109.3, 108.9, 108.8, 107.9, 81.2, 56.2, 37.5, 9.8; MS (ES+) m/z 462.9 (M+23).

Workup

  1. stirringThe mixture was stirred at ambient temperature for 20 h
  2. washwashed with water and brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated in vacuum
  6. customThe residue was purified by column chromatography with ethyl acetate in hexanes (10% to 40% gradient)

Sources & evidence

ORD record
ord-967803c4bda4403ab2f31be35be72e08
Source dataset
uspto-grants-2013_04
Patent number
US08415370B2

Reaction notes

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