Acetovanillone → 1-(2-Amino-4-(benzyloxy)-5-methoxyphenyl)ethanone

1-(4-Hydroxy-3-methoxyphenyl)-1-ethanone (20 g), potassium carbonate (18.3 g), tetra-n-butylammonium iodide (4.45 g), and benzyl bromide (17.3 ml) were dissolved in N,N-dimethylformamide (300 ml), and a reaction was allowed to proceed at 100° C. for one hr. The solvent was removed by distillation under the reduced pressure, and water was added to the residue, followed by extraction with ethyl acetate. The ethyl acetate layer was dried over sodium sulfate. Next, the solvent was removed by distillation under the reduced pressure. The residue and fuming nitric acid (12.47 ml) were dissolved in acetic acid (120 ml), and a reaction was allowed to proceed at room temperature for 2 hr. The reaction solution was neutralized at 0° C. by the addition of an aqueous sodium hydroxide solution, followed by extraction with chloroform. The chloroform layer was then dried over sodium sulfate. Next, the solvent was removed by distillation under the reduced pressure. The residue was dissolved in ethanol (1160 ml) and water (120 ml) with heating. Ammonium chloride (19.2 g) and zinc (101.7 g) were added thereto. The mixture was heated under reflux for 3 hr. The reaction solution was filtered through Celite, followed by washing with chloroform/methanol (3/1). The solvent was removed by distillation under the reduced pressure, and the residue was made alkaline with an aqueous sodium hydroxide solution, and the alkaline solution was extracted with chloroform. The chloroform layer was dried over sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by chromatography on silica gel by development with chloroform/ethyl acetate (10/1) to give 24.95 g (yield 77%) of the title compound (3 steps).

1. customThe solvent was removed by distillation under the reduced pressure, and water
2. additionwas added to the residue
3. extractionfollowed by extraction with ethyl acetate
4. dry with materialThe ethyl acetate layer was dried over sodium sulfate
5. customNext, the solvent was removed by distillation under the reduced pressure
6. dissolutionThe residue and fuming nitric acid (12.47 ml) were dissolved in acetic acid (120 ml)
7. waitto proceed at room temperature for 2 hr
8. additionThe reaction solution was neutralized at 0° C. by the addition of an aqueous sodium hydroxide solution
9. extractionfollowed by extraction with chloroform
10. dry with materialThe chloroform layer was then dried over sodium sulfate
11. customNext, the solvent was removed by distillation under the reduced pressure
12. dissolutionThe residue was dissolved in ethanol (1160 ml)
13. temperaturewater (120 ml) with heating
14. additionAmmonium chloride (19.2 g) and zinc (101.7 g) were added
15. temperatureThe mixture was heated
16. temperatureunder reflux for 3 hr
17. filtrationThe reaction solution was filtered through Celite
18. washby washing with chloroform/methanol (3/1)
19. customThe solvent was removed by distillation under the reduced pressure
20. extractionthe alkaline solution was extracted with chloroform
21. dry with materialThe chloroform layer was dried over sodium sulfate
22. customThe solvent was removed by distillation under the reduced pressure
23. customthe residue was purified by chromatography on silica gel by development with chloroform/ethyl acetate (10/1)

ORD record

ord-c6300c10fbfb48899cf5f2d74a3a12a3

Source dataset

uspto-grants-2007_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07169789B2