Dimethylformamide → 4-Hydroxy-2,5-dimethoxybenzaldehyde

POCl3 was added dropwise (T<20° C.) to a solution of intermediate 57, 2,5-Dimethoxyphenol (10.8 g, 0.07 mol) in DMF (22 mL, 0.28 mol) under vigorous stirring and cooling with an ice bath. The reaction mixture was stirred at room temperature for 72 h, then at 50° C. for 48 h, cooled, and diluted with H2O and ether (50 mL each). The solution was alkalized to pH 6 with a 10 N solution of NaOH. The aqueous layer was separated and subjected to extraction with ether. The combined extracts were dried and evaporated. The residue was recrystallized from ether. The obtained crystals were dissolved under argon in MeOH (20 mL). NaOH (0.5 g, 12 mmol) was added, and the mixture was stirred for 12 h. Then pH was brought to 6 with a 5 M solution of NaHSO4 (2.4 mL), and the mixture was evaporated. The residue was dissolved in CHCl3. The solution was washed with H2O, dried, and evaporated to give the title compound (1.2 g, 10%) as yellow crystals. 1H NMR data (DMSO-d6): 10.37 (s, 1H, —COH), 10.14 (s, 1H, Ar—OH), 7.17 (s, 1H, Ar—H), 6.60 (s, 1H, Ar—H), 3.81 (s, 3H, —OCH3), 3.76 (s, 3H, —OCH3).

1. temperaturecooling with an ice bath
2. stirringThe reaction mixture was stirred at room temperature for 72 h
3. temperaturecooled
4. customThe aqueous layer was separated
5. extractionsubjected to extraction with ether
6. customThe combined extracts were dried
7. customevaporated
8. customThe residue was recrystallized from ether
9. dissolutionThe obtained crystals were dissolved under argon in MeOH (20 mL)
10. stirringthe mixture was stirred for 12 h
11. customthe mixture was evaporated
12. dissolutionThe residue was dissolved in CHCl3
13. washThe solution was washed with H2O
14. customdried
15. customevaporated

ORD record

ord-bd285d21dc9f49e0aab9e7a22a35955d

Source dataset

uspto-grants-2010_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07812040B2