Acetic Acid → 4-Methoxy-3,5-dimethylpyridine 1-Oxide

Temperature

90 °C

3,5-lutidine (15 kg, 140.2 moles) was dissolved in acetic acid (48 l) at 60° C. Hydrogen peroxide (8430 ml, 98 moles) was added during 3 hours. The solution was heated to 90° C. and kept at this temperature for 3 hours. The reaction mixture was cooled to 60° C. and hydrogen peroxide (3500 ml, 41 moles) was added during 1 hour. The temperature was raised to 90° C. and kept there for 16 hours. The reaction mixture was evaporated at reduced pressure (70° C. 300 mm Hg). The residue (approx 25 liters) was cooled and pH adjusted to 10 with NaOH-solution (23 liters 10M). Acetonitrile (30 liters) was added and the mixture was stirred for 30 minutes. The sodiumacetate was separated off and washed with 10 l acetonitrile. The liquid phase was evaporated at reduced pressure (55° C., 200 mm Hg). The remaining solution (approx 25 liters) was extracted with CH2Cl2 (20 liters and 3×5 liters). The combined organic layers were dried over MgSO4, filtrated and evaporated at reduced pressure (50° C. 200 mm Hg). When all CH2Cl2 had distilled off unreacted 3,5-lutidine was evaporated at 75° C., 8 mm Hg. Yield 14940 g of 3,5-dimethylpyridine-N-oxide. The identity was confirmed with 1 H and 13C NMR.

1. temperatureThe reaction mixture was cooled to 60° C.
2. temperatureThe temperature was raised to 90° C.
3. waitkept there for 16 hours
4. customThe reaction mixture was evaporated at reduced pressure (70° C. 300 mm Hg)
5. temperatureThe residue (approx 25 liters) was cooled
6. additionAcetonitrile (30 liters) was added
7. customThe sodiumacetate was separated off
8. washwashed with 10 l acetonitrile
9. customThe liquid phase was evaporated at reduced pressure (55° C., 200 mm Hg)
10. extractionThe remaining solution (approx 25 liters) was extracted with CH2Cl2 (20 liters and 3×5 liters)
11. dry with materialThe combined organic layers were dried over MgSO4
12. filtrationfiltrated
13. customevaporated at reduced pressure (50° C. 200 mm Hg)
14. distillationWhen all CH2Cl2 had distilled off unreacted 3,5-lutidine
15. customwas evaporated at 75° C.

ORD record

ord-0badf35745d94f0c929fc1443db4140f

Source dataset

uspto-grants-1985_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04544750