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

HRID 1528041Notes

Reaction equation

HRID 1528041 reaction equation
[OH:1][C:2]1[C:7]([CH2:8][CH:9]=[C:10]([CH3:12])[CH3:11])=[C:6]([OH:13])[C:5]([CH2:14][CH:15]=[C:16]([CH3:18])[CH3:17])=[C:4](O)[C:3]=1[C:20](=[O:23])[CH2:21][CH3:22].C(=O)([O-])[O-].[K+].[K+].[F:30][C:31]1[CH:32]=[C:33]([CH:37]=[CH:38][C:39]=1[Cl:40])[C:34](Cl)=[O:35]>CCCC[N+](CCCC)(CCCC)CCCC.[Br-].C1(C)C=CC=CC=1>[F:30][C:31]1[CH:32]=[C:33]([C:34]2[O:35][C:4]3[C:5]([CH2:14][CH:15]=[C:16]([CH3:18])[CH3:17])=[C:6]([OH:13])[C:7]([CH2:8][CH:9]=[C:10]([CH3:12])[CH3:11])=[C:2]([OH:1])[C:3]=3[C:20](=[O:23])[C:21]=2[CH3:22])[CH:37]=[CH:38][C:39]=1[Cl:40]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 38662994-Chloro-3-fluorobenzoyl chlorideHCID 867022171-[2,4,6-Trihydroxy-3,5-di(3-methyl-2-buten-1-yl)phenyl]propan-1-one

Product 1

HCID 867022182-(3-fluoro-4-chlorophenyl)-3-methyl-5,7-dihydroxy-6,8-di(3-methyl-2-buten-1-yl)-4H-benzopyran-4-oneYield 1.9%

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 1140TolueneSolvent

Procedure

Under nitrogen atmosphere, 1-[2,4,6-trihydroxy-3,5-di(3-methyl-2-buten-1-yl)phenyl]propan-1-one (300 mg, 0.943 mmol), anhydrous potassium carbonate powder (817 mg, 5.91 mmol), TBAB (tetrabutyl ammonium bromide, 477 mg, 1.47 mmol) and 3-fluoro-4-chlorobenzoyl chloride (380 mg, 1.97 mmol) were dissolved in toluene (30 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 5% potassium carbonate aqueous solution and heated to reflux for 2 hr. After cooling to ambient temperature, the mixture was acidified to pH 6 with 1N HCl solution, and extracted with dichloromethane three times. The combined organic phase was dried over anhydrous sodium sulfate, and the solvent was removed. The crude product was purified by silica gel column chromatography (eluent:ethyl acetate/petroleum ether, 1:50) and recrystallized in ethanol to give the desired compound (8 mg, yield 1.9%). 1H NMR (400 MHz, CDCl3): δ=13.10 (s, 1H), 7.56 (d, 1H, J=7.6 Hz), 7.43 (dd, 1H, J1=9.6 Hz, J2=1.6 Hz), 7.37 (d, 1H, J=1.6 Hz), 6.35 (s, 1H), 5.28-5.17 (m, 2H), 3.47 (d, 2H, J=7.2 Hz), 3.44 (d, 2H, J=7.2 Hz), 2.14 (s, 3H), 1.84 (s, 3H), 1.77 (s, 3H), 1.73 (s, 3H), 1.72 (s, 3H); LC-MS (ESI) m/z 457.9 [M+H]+.

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 5% potassium carbonate aqueous solution
  11. temperatureheated
  12. temperatureto reflux for 2 hr
  13. extractionextracted with dichloromethane three times
  14. dry with materialThe combined organic phase was dried over anhydrous sodium sulfate
  15. customthe solvent was removed
  16. customThe crude product was purified by silica gel column chromatography (eluent:ethyl acetate/petroleum ether, 1:50)
  17. customrecrystallized in ethanol

Sources & evidence

ORD record
ord-270ce0679bb845ba8f1dce2efae4c8b0
Source dataset
uspto-grants-2015_07
Patent number
US09090583B2

Reaction notes

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