Potassium Carbonate → 2-(3-fluoro-4-methoxyphenyl)-5,7-dihydroxy-3-methoxy-6,8-di(3-methyl-2-buten-1-yl)-4H-benzopyran-4-one

HRID 1528035Notes

Reaction equation

HRID 1528035 reaction equation
[CH3:1][O:2][CH2:3][C:4]([C:6]1[C:11]([OH:12])=[C:10]([CH2:13][CH:14]=[C:15]([CH3:17])[CH3:16])[C:9]([OH:18])=[C:8]([CH2:19][CH:20]=[C:21]([CH3:23])[CH3:22])[C:7]=1[OH:24])=[O:5].C(=O)([O-])[O-].[K+].[K+].[F:31][C:32]1[CH:33]=[C:34]([CH:38]=[CH:39][C:40]=1[O:41][CH3:42])[C:35](Cl)=O>CCCC[N+](CCCC)(CCCC)CCCC.[Br-].C1(C)C=CC=CC=1>[F:31][C:32]1[CH:33]=[C:34]([C:35]2[O:24][C:7]3[C:8]([CH2:19][CH:20]=[C:21]([CH3:23])[CH3:22])=[C:9]([OH:18])[C:10]([CH2:13][CH:14]=[C:15]([CH3:17])[CH3:16])=[C:11]([OH:12])[C:6]=3[C:4](=[O:5])[C:3]=2[O:2][CH3:1])[CH:38]=[CH:39][C:40]=1[O:41][CH3:42]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 27792553-Fluoro-4-methoxybenzoyl chlorideHCID 867022152-Methoxy-1-[2,4,6-trihydroxy-3,5-di(3-methyl-2-buten-1-yl)phenyl]ethanone

Product 1

HCID 574050422-(3-fluoro-4-methoxyphenyl)-5,7-dihydroxy-3-methoxy-6,8-di(3-methyl-2-buten-1-yl)-4H-benzopyran-4-oneYield 32.8%

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 1140TolueneSolvent

Procedure

Under nitrogen atmosphere, 2-methoxy-1-[2,4,6-trihydroxy-3,5-di(3-methyl-2-buten-1-yl)phenyl]ethanone (300 mg, 0.897 mmol), anhydrous potassium carbonate powder (744 mg, 5.38 mmol), TBAB (tetrabutyl ammonium bromide, 434 mg, 1.346 mmol), and 3-fluoro-4-methoxybenzoyl chloride (388 mg, 2.057 mmol) were dissolved in toluene (84 mL), and refluxed for 6 hours. After cooling, toluene was removed, and then water (20 mL) was added. The aqueous solution was extracted with ethyl acetate. The combined organic phase was washed with water and saturated brine, and dried over anhydrous sodium sulfate. A brown residue was obtained after removal of solvent. The residue was dissolved in a 20 mL methanol-H2O (4:1) mixture, to which was added potassium hydroxide (1 g). The mixture was heated to reflux for 2 hours, then cooled to ambient temperature, acidified to pH 4 with 1N HCl solution, and extracted with dichloromethane three times. The combined organic phase was dried over anhydrous sodium sulfate, with removal of solvent. The crude product was purified by silica gel column chromatography (eluent: ethyl acetate/petroleum ether, 1:50) to give the desired compound (137.8 mg, yield 32.6%). 1H NMR (400 MHz, CDCl3): δ=12.89 (s, 1H), 7.94 (dt, 1H, J1=8.8 Hz, J2=2.0 Hz), 7.90 (dd, 1H, J1=8.8 Hz, J2=2.0 Hz), 7.08 (t, 1H, J=8.8 Hz), 6.36 (s, 1H), 5.27-5.23 (m, 2H), 3.99 (s, 3H,), 3.88 (s, 3H), 3.54 (d, 2H, J=6.8 Hz), 3.47 (d, 2H, J=6.8 Hz), 1.85 (s, 3H), 1.84 (s, 3H), 1.77 (s, 3H), 1.75 (s, 3H); LC-MS (ESI) m/z 469.5 [M+14]+.

Workup

  1. temperaturerefluxed for 6 hours
  2. temperatureAfter cooling
  3. customtoluene was removed
  4. additionwater (20 mL) was added
  5. extractionThe aqueous solution was extracted with ethyl acetate
  6. washThe combined organic phase was washed with water and saturated brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. customA brown residue was obtained
  9. customafter removal of solvent
  10. dissolutionThe residue was dissolved in a 20 mL methanol-H2O (4:1) mixture, to which
  11. additionwas added potassium hydroxide (1 g)
  12. temperatureThe mixture was heated
  13. temperatureto reflux for 2 hours
  14. extractionextracted with dichloromethane three times
  15. dry with materialThe combined organic phase was dried over anhydrous sodium sulfate, with removal of solvent
  16. customThe crude product was purified by silica gel column chromatography (eluent: ethyl acetate/petroleum ether, 1:50)

Sources & evidence

ORD record
ord-45c0774bde594f29ac9237342c368224
Source dataset
uspto-grants-2015_07
Patent number
US09090583B2

Reaction notes

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