3,4,5-Trimethoxybenzaldehyde → 5,6,7-Trimethoxynaphthalene-2-carbonitrile

Temperatur

-75 °C

2.0 M Lithium diisopropylamide (2.55 mL) was added to dry THF (5 mL) at −75° C. under an argon atmosphere, and a solution of 3-cyanopropionaldehyde dimethylacetal (672 mg) in dry THF (5 mL) was then added dropwise to the mixture, and the resulting mixture was stirred at −75° C. for 1 hour. A solution of 3,4,5-trimethoxy-benzaldehyde (1.0 g) in dry THF (5 mL) was then added dropwise to the reaction mixture. After the mixture was warmed to room temperature and stirred for 1 hour, a saturated aqueous solution of ammonium chloride was added to the reaction mixture to conduct extraction with ethyl acetate. The resultant organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The resultant residue was dissolved in methanol (6 mL), sulfuric acid (1 mL) was slowly added to the solution, and the mixture was stirred at 100° C. for 1 hour. The reaction mixture was weakly alkalified with an aqueous solution of 4 M potassium hydroxide at 0° C. to conduct extraction with chloroform. The resultant organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (ethyl acetate:hexane=1:3 to 1:1) to obtain the title compound.

1. temperatureAfter the mixture was warmed to room temperature
2. stirringstirred for 1 hour
3. extractionextraction with ethyl acetate
4. washThe resultant organic layer was washed with saturated brine
5. dry with materialdried over anhydrous magnesium sulfate
6. concentrationconcentrated under reduced pressure
7. dissolutionThe resultant residue was dissolved in methanol (6 mL)
8. additionsulfuric acid (1 mL) was slowly added to the solution
9. stirringthe mixture was stirred at 100° C. for 1 hour
10. customwas weakly alkalified with an aqueous solution of 4 M potassium hydroxide at 0° C.
11. extractionextraction with chloroform
12. washThe resultant organic layer was washed with water and saturated brine
13. dry with materialdried over anhydrous magnesium sulfate
14. concentrationconcentrated under reduced pressure
15. customThe residue was purified by column chromatography on silica gel (ethyl acetate:hexane=1:3 to 1:1)

ORD-Eintrag

ord-37262d66556b4295ae4a4c3b88d8e96a

Quelldatensatz

uspto-grants-2003_04

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06552188B2