Hydrochloric Acid → 2-(3,4-Dimethoxyphenyl)-7-hydroxy-4H-chromen-4-one

Temperature

0 °C

Dry, pulverulent lithium hydroxide (18 mmol, 3.6 equivalents) is added in one portion to a well-stirred solution of 2,4-dihydroxyacetophenone (5 mmol) in dry THF (5 ml) under an argon atmosphere at −78° C. The reaction mixture is stirred at −78° C. for one hour and subsequently at about 0° C. for two hours. After the mixture has been re-cooled to −78° C., a solution of 3,4-dimethoxybenzoyl chloride (5.9 mmol) in THF (10 ml) is added in one portion. The mixture is stirred at −78° C. for one hour and at room temperature for 4 hours until the starting material has disappeared. The reaction mixture is emptied into a mixture of ice (150 g) and concentrated HCl (5 ml) and extracted with chloroform (3×50 ml). The solvents are removed from the dried extracts, and the residue is dried under reduced pressure for 24 hours. Glacial acetic acid (30 ml) and sulfuric acid (0.2 ml) are added to the residue, and the mixture is heated at 95–100° C. for from 30 minutes to one hour under an argon atmosphere. Approximately one third of the acetic acid is stripped off, and the residue is emptied into water. The precipitated product is filtered, washed and dried and recrystallised in methanol, giving 3′,4′-dimethoxy-7-hydroxyflavone. 1H NMR (250 MHz, DMSO-d6): δ=3.85 (d, 6 H), 6.85–8.00 (m, 7 H), 10.72 (s, 1 H); 13C NMR (250 MHz, DMSO-d6): δ=56.08 (s), 56.22 (s), 102.95 (s), 105.82 (s), 109.76 (s), 112.11 (s), 115.19 (s), 116.51 (s), 119.38 (s), 123.97 (s), 126.80 (s), 149.40 (s), 152.10 (s), 157.79 (s), 162.41 (s), 162.94 (s), 176.70 (s); EI-MS (70 eV) m/e (rel. abund.)=298; UV (2-propanol): λ=236 nm, 332 nm.

1. customDry
2. temperatureAfter the mixture has been re-cooled to −78° C.
3. stirringThe mixture is stirred at −78° C. for one hour and at room temperature for 4 hours until the starting material
4. extractionextracted with chloroform (3×50 ml)
5. customThe solvents are removed from the dried extracts
6. customthe residue is dried under reduced pressure for 24 hours
7. additionGlacial acetic acid (30 ml) and sulfuric acid (0.2 ml) are added to the residue
8. temperaturethe mixture is heated at 95–100° C. for from 30 minutes to one hour under an argon atmosphere
9. filtrationThe precipitated product is filtered
10. washwashed
11. customdried
12. customrecrystallised in methanol

ORD record

ord-a772936a976f4508bb2f3db2921f2fab

Source dataset

uspto-grants-2006_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07009062B2