4-chloro-3-fluorobenzoyl chloride

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

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]+. refluxed for 6 hours After cooling toluene was removed water (20 mL) was added The aqueous solution was extracted with ethyl acetate The combined organic phase was washed with water and saturated brine 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 heated to reflux for 2 hr extracted with dichloromethane three times The combined organic phase was dried over anhydrous sodium sulfate the solvent was removed The crude product was purified by silica gel column chromatography (eluent:ethyl acetate/petroleum ether, 1:50) recrystallized in ethanol

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under nitrogen atmosphere, 1-[2,4,6-trihydroxy-3,5-di(3-methyl-2-buten-1-yl)phenyl]ethanone (300 mg, 0.986 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) to give the desired compound (15 mg, yield 3.5%). 1H NMR (400 MHz, CDCl3): δ=12.90 (s, 1H), 7.67-7.55 (m, 3H), 6.62 (s, 1H), 6.43 (s, 1H), 5.27-5.24 (m, 2H), 3.54 (d, 2H, J=6.8 Hz), 3.47 (d, 2H, J=6.8 Hz), 1.85 (s, 3H), 1.81 (s, 3H), 1.78 (s, 3H), 1.76 (s, 3H); LC-MS (ESI) m/z 473.6 [M+H]+. refluxed for 6 hours After cooling toluene was removed water (20 mL) was added The aqueous solution was extracted with ethyl acetate The combined organic phase was washed with water and saturated brine 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 heated to reflux for 2 hr extracted with dichloromethane three times The combined organic phase was dried over anhydrous sodium sulfate the solvent was removed The crude product was purified by silica gel column chromatography (eluent:ethyl acetate/petroleum ether, 1:50)