Nitric Acid → Dimethyl 4-methyl-5-nitrophthalate

Temperatur

80 °C

A, B: 4-Methylphthalic anhydride 9a (67.5 mmol, 10.94 g) and concentrated sulfuric acid (10 mL) were placed in a three-necked round-bottomed flask and the mixture was stirred mechanically at 80° C. A mixture of fuming nitric acid (d=1.5, 4.2 mL) and concentrated sulfuric acid (3.0 mL) was added slowly from a dropping funnel at such a rate as to maintain the temperature of the stirred mixture at 100-110° C. Then concentrated nitric acid (d=1.42, 18 mL) was added as rapidly as possible without causing the temperature to rise above 110° C. The reaction mixture was heated at 100° C. for two hours, allowed to stand at room temperature for 16 h and poured into 30 mL of water. The white precipitate was filtered off and the filtrate was extracted with ethyl ether. The organic phase was dried with magnesium sulfate, filtered and concentrated under vacuum. The residual solid (13 g) was dissolved in N,N-dimethylformamide (50 mL) containing potassium carbonate (0.12 mol, 16.9 g). Dimethyl sulfate (0.12 mol, 15.4 g, 11.5 mL) was added and the mixture was stirred magnetically at room temperature for two hours. N,N-dimethylformamide was evaporated under reduced pressure. The residue was dissolved in ethyl acetate and the organic phase was washed with water, brine and dried with magnesium sulfate. The salts were filtered off and the filtrate was concentrated under vacuum. The residue was purified by flash chromatography on type H silica gel using hexane/ethyl acetate (4/1) as eluent to yield 5.26 g (31%) of dimethyl 4-methyl-5-nitrophthalate 9c as a white solid.

1. additionwas added slowly from a dropping funnel at such a rate as
2. temperatureto maintain the temperature of the stirred mixture at 100-110° C
3. customto rise above 110° C
4. temperatureThe reaction mixture was heated at 100° C. for two hours
5. filtrationThe white precipitate was filtered off
6. extractionthe filtrate was extracted with ethyl ether
7. dry with materialThe organic phase was dried with magnesium sulfate
8. filtrationfiltered
9. concentrationconcentrated under vacuum
10. dissolutionThe residual solid (13 g) was dissolved in N,N-dimethylformamide (50 mL)
11. stirringthe mixture was stirred magnetically at room temperature for two hours
12. customN,N-dimethylformamide was evaporated under reduced pressure
13. dissolutionThe residue was dissolved in ethyl acetate
14. washthe organic phase was washed with water, brine
15. dry with materialdried with magnesium sulfate
16. filtrationThe salts were filtered off
17. concentrationthe filtrate was concentrated under vacuum
18. customThe residue was purified by flash chromatography on type H silica gel

ORD-Eintrag

ord-91bd69d24dd9416982e298048936cd87

Quelldatensatz

uspto-grants-2004_07

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06759409B2