Triethylamine → N-(2-fluorophenyl)-2-(2'-oxo-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3'-indol]-1'(2'H)-yl)acetamide

HRID 1407903Notes

Reaction equation

HRID 1407903 reaction equation
[O:1]=[C:2]1[C:10]2([C:22]3[C:13](=[CH:14][C:15]4[O:20][CH2:19][CH2:18][O:17][C:16]=4[CH:21]=3)[O:12][CH2:11]2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]1[CH2:23][C:24](O)=[O:25].[F:27][C:28]1[CH:34]=[CH:33][CH:32]=[CH:31][C:29]=1[NH2:30].C(N(CC)CC)C.C(OC1C=CC2C(=CC=CC=2)N1C(OCC)=O)C>C(Cl)(Cl)Cl.C(OCC)(=O)C>[F:27][C:28]1[CH:34]=[CH:33][CH:32]=[CH:31][C:29]=1[NH:30][C:24](=[O:25])[CH2:23][N:3]1[C:4]2[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=2)[C:10]2([C:22]3[C:13](=[CH:14][C:15]4[O:20][CH2:19][CH2:18][O:17][C:16]=4[CH:21]=3)[O:12][CH2:11]2)[C:2]1=[O:1]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 95842-FluoroanilineHCID 278332-Ethoxy-1-(ethoxycarbonyl)-1,2-dihydroquinolineHCID 59352547(2'-oxo-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3'-indol]-1'(2'H)-yl)acetic acid

Product 1

HCID 59352416N-(2-fluorophenyl)-2-(2'-oxo-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3'-indol]-1'(2'H)-yl)acetamideYield 12%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (2′-oxo-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3′-indol]-1′(2′H)-yl)acetic acid (0.53 g, 1.50 mmol), 2-fluoroaniline (0.2 mL, 2.1 mmol) and triethylamine (0.5 mL, 3.5 mmol) in chloroform (30 mL) was added 2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline (0.48 g, 1.94 mmol). The reaction mixture was heated at reflux for 26 h, allowed to cool to ambient temperature, diluted with ethyl acetate and washed sequentially with water, 10% w/v hydrochloric acid, water, 10% w/v aqueous sodium hydroxide, water and brine. The organic phase was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo. The residue was purified by column chromatography and eluted with ethyl acetate/hexanes (1/3) to afford N-(2-fluorophenyl)-2-(2′-oxo-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3′-indol]-1′(2′H)-yl)acetamide (0.08 g, 12%): mp 117-119° C. (ethyl acetate/hexanes); 1H NMR (300 MHz, CDCl3) δ 8.24-8.22 (m, 1H), 8.05-7.90 (m, 1H), 7.33-6.95 (m, 6H), 6.50-6.47 (m, 1H), 6.33-6.30 (m, 1H), 4.94-4.89 (m, 1H), 4.68-4.49 (m, 4H), 4.17-4.09 (m, 4H); 13C NMR (75 MHz, CDCl3) δ 178.2, 164.6, 155.2, 144.7, 141.3, 138.4, 131.9, 129.1, 125.6, 124.9, 121.8, 120.4, 115.0, 114.8, 111.7, 108.9, 99.4, 80.0, 64.6, 63.8, 58.0, 45.1; MS (ES+) m/z 446.8 (M+1).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 26 h
  3. washwashed sequentially with water, 10%
  4. dry with materialThe organic phase was dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated in vacuo
  7. customThe residue was purified by column chromatography
  8. washeluted with ethyl acetate/hexanes (1/3)

Sources & evidence

ORD record
ord-9c18e930a12e421690d43c211072c168
Source dataset
uspto-grants-2014_12
Patent number
US08916580B2

Reaction notes

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