Hydrochloric Acid → 3,3,6-Trimethyl-1,3-dihydrofuro[3,4-c]pyridin-7-ol

Into a 3-liter reactor fitted with stirring, warming and cooling means, previously submitted to a nitrogen circulation, were poured 3.47 g (0.143 mol) of magnesium. Slowly, under stirring, there was then added 20.3 g (0.143 mol) of methyl iodide dissolved in 400 ml of distilled diethyl ether. The mixture was refluxed for 2 to 3 hours, then cooled to 10°-15° C. and 22.8 g (0.11 mol of α4, 3-o-isopropylidene pyridoxal dissolved in 600 ml of distilled diethyl ether were slowly added. The mixture was stirred for 12 hours at room temperature, and then the diethyl ether was evaporated off under reduced pressure (end of preparation of starting secondary alcohol). 450 ml of dry methylene dichloride with 30.5 g (0.142 mol) of pyridinium chlorochromate and 2.35 g (0.0285 mol) of pure and dry sodium acetate were poured all at once into the reactor and the mixture was stirred for 2 hours at room temperature, and then for some minutes, after addition of 200 ml of dry diethyl ether. After elimination of insoluble matter, the organic phase was filtered and evaporated to dryness, leading to an oily product (end of step (ii)). This product was dissolved in 400 ml of diethyl ether and treated under stirring for 12 hours at room temperature with a mixture obtained by refluxing for 2 hours 400 ml of diethyl ether, 20 g (0.14 mol) of methyl iodide and 3.45 g (0.14 mol) of magnesium. The diethyl ether was evaporated off under reduced pressure; after cooling, there were added 0.5 l of chloroform and, dropwise, under stirring, 150 ml of 2N hydrochloric acid. Stirring was maintained for 2 hours, the mixture was decanted, the precipitate washed with water, dried on anhydrous sodium sulphate, redissolved in diethyl ether, recrystallized, washed and dried (end of step (iii)). The compound thus obtained was then treated with 100 ml of concentrated hydrochloric acid at room temperature, under stirring for 12 hours. The precipitate obtained was treated twice by ethanol and recrystallized from acetone. Yield 15.9 g (67%) of a pale yellow product melting at 247° C. (Tottoli), elemental analysis of which showed good correspondence with the formula C10H13NO2HCl. The product exhibited good solubility in water at room temperature.

1. customInto a 3-liter reactor fitted
2. temperaturewarming
3. temperaturecooling means
4. stirringSlowly, under stirring
5. temperatureThe mixture was refluxed for 2 to 3 hours
6. temperaturecooled to 10°-15° C.
7. additionwere slowly added
8. stirringThe mixture was stirred for 12 hours at room temperature
9. customthe diethyl ether was evaporated off under reduced pressure (end of preparation of starting secondary alcohol)
10. stirringthe mixture was stirred for 2 hours at room temperature
11. waitfor some minutes
12. filtrationAfter elimination of insoluble matter, the organic phase was filtered
13. customevaporated to dryness
14. dissolutionThis product was dissolved in 400 ml of diethyl ether
15. additiontreated
16. stirringunder stirring for 12 hours at room temperature with a mixture
17. customobtained
18. customThe diethyl ether was evaporated off under reduced pressure
19. temperatureafter cooling
20. additionthere were added 0.5 l of chloroform
21. stirringdropwise, under stirring
22. stirringStirring
23. temperaturewas maintained for 2 hours
24. customthe mixture was decanted
25. washthe precipitate washed with water
26. dry with materialdried on anhydrous sodium sulphate
27. dissolutionredissolved in diethyl ether
28. customrecrystallized
29. washwashed
30. customdried (end of step (iii))
31. customThe compound thus obtained
32. stirringunder stirring for 12 hours
33. customThe precipitate obtained
34. customrecrystallized from acetone
35. customat room temperature

ORD record

ord-7330b8c0dc6c46e38d589a3b3511ac7b

Source dataset

uspto-grants-1986_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04581363