2-(Bromomethyl)acrylic acid ethyl ester → 8-[(2,3,4,5-Tetrahydro-2-methyl-4-methylene-5-oxo-2-furanyl)methoxy]-2(1H)-quinolinone

HRID 263964Notes

Reaction equation

HRID 263964 reaction equation
C([O:4][C:5]1[CH:14]=[CH:13][C:12]2[C:7](=[C:8]([O:15][CH2:16]C(=O)C)[CH:9]=[CH:10][CH:11]=2)[N:6]=1)(=O)C.Br[CH2:21][C:22](=[CH2:28])[C:23]([O:25][CH2:26][CH3:27])=[O:24].C([O-])(O)=O.[Na+]>O1CCCC1.[Zn].C1(C=CC(O)=CC=1)O>[CH3:27][C:26]1([CH2:16][O:15][C:8]2[CH:9]=[CH:10][CH:11]=[C:12]3[C:7]=2[NH:6][C:5](=[O:4])[CH:14]=[CH:13]3)[CH2:21][C:22](=[CH2:28])[C:23](=[O:24])[O:25]1

Participants

7

Reactant 3

HCID 3106202-(Bromomethyl)acrylic acid ethyl esterHCID 516892Sodium BicarbonateHCID 190360332-Acetoxy-8-(2-oxopropoxy)quinoline

Product 1

HCID 103565758-[(2,3,4,5-Tetrahydro-2-methyl-4-methylene-5-oxo-2-furanyl)methoxy]-2(1H)-quinolinoneYield 68.9%

Reagents, catalysts & solvents 3

HCID 785HydroquinoneCatalystHCID 23994ZincCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 5c (0.78 g, 3 mmol) in dry tetrahydrofuran (60 ml) were added activated zinc powder (0.26 g, 3.9 mmol), hydroquinone (6 mg), and ethyl 2-(bromomethyl)acrylate (0.78 g, 4 mmol). The mixture was refluxed under nitrogen atmosphere for 6 h (monitored by TLC). After cooling, it was poured into an ice-cold 5% HCl solution (300 ml), neutralized with 1.0N NaHCO3, and extracted with CH2Cl2 (75 ml×3). The dichloromethane extracts were combined and washed with water, dried over Na2SO4, and then evaporated to give a residual oil which was purified by column chromatography on silica gel using CH2Cl2 as the eluent to afford the title compound (0.59 g, 60%). UV λmax (log ε): 258 (4.70) (0.1N HCl in MeOH), 246 (4.69) (MeOH), 261 (4.59) (0.1N NaOH in MeOH); 1H-NMR (CDCl3): δ1.61 (s, 3H, 2'-CH3), 2.78 (dt, 1H, 3'-H), 3.17 (dt, 1H, 3'-H), 4.50 (s, 2H, OCH2), 5.65 (t, 1H, vinylic H), 6.29 (t, 1H, vinylic H), 6.91 (d, 1H, 3-H), 7.18-7.41 (m, 3H, Ar--H), 8.02 (d, 1H, 4-H). Anal Calcd for C16H15NO4 : C, 67.36; H, 5.30; N, 4.91. Found: C, 67.38; H, 5.32; N, 5.00.

Workup

  1. temperatureThe mixture was refluxed under nitrogen atmosphere for 6 h (monitored by TLC)
  2. temperatureAfter cooling
  3. extractionextracted with CH2Cl2 (75 ml×3)
  4. washwashed with water
  5. dry with materialdried over Na2SO4
  6. customevaporated
  7. customto give a residual oil which
  8. customwas purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-fbc20eeed277451284034193478081ac
Source dataset
uspto-grants-1997_07
Patent number
US05646164

Reaction notes

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