Methanol → 2,6-Bis(tert-butylamino)-4-methylpyridin-3-yl methyl ketone

Temperature

5 °C

3.17 g. (20.3 mmol.) of the amidine of Formula XIII (the product of Example 2) were suspended in 20 ml. of tetrahydrofuran and 12.7 ml. of a 1.6 M. solution of n-butyl lithium in hexane were added under nitrogen. The resulting exothermic reaction yielded a solution having a temperature of about 40° C. This solution was stirred at 30°-40° C. for 45 minutes and a solution of 2.80 g. (20.3 mmol.) of Compound XIV (Woodward et al., J. Amer. Chem. Soc. 88, 3169-3170 (1966).) in 8 ml. of tetrahydrofuran was added at 30°-38° C. followed by an additional 2 ml. of tetrahydrofuran. After 10 minutes a precipiate began to form. Stirring was contained for an additional 35 minutes and the reaction mixture was allowed to stand overnight. (Thin layer chromatographs of the reaction mixture after 45 minutes and the following morning were the same). The reaction mixture was cooled to - 5° C. and 2 ml. of saturated ammonium chloride solution were added. Sufficient chloroform and a trace of methanol were added to form a solution which was evaporated at reduced pressure to obtain a mixture of oil and solids. This mixture was distributed between chloroform and water and a small amount (about 1/2 g.) of a white insoluble material was filtered off. The aqueous phase was re-extracted with chloroform and the chloroform phase was combined with the chloroform phase of the initial distribution. The combined chloroform phases were dried over anhydrous magnesium sulfate, filtered and evaporated to a brown oil (about 5 1/2 g.). The brown oil was dissolved in a small volume of methanol at 40° C. and water was added until the resulting cloudiness persisted. The desired product crystallized out in the form of yellow needles which were washed with a small amount of a 1:1 mixture of methanol and water, m.p. 127°-128° C. Yield: 1.791 g.

1. customThe resulting exothermic reaction
2. customyielded a solution
3. customa temperature of about 40° C
4. waitAfter 10 minutes a precipiate began
5. customto form
6. stirringStirring
7. waitwas contained for an additional 35 minutes
8. waitto stand overnight
9. wait(Thin layer chromatographs of the reaction mixture after 45 minutes
10. customto form a solution which
11. customwas evaporated at reduced pressure
12. customto obtain
13. additiona mixture of oil and solids
14. filtrationa small amount (about 1/2 g.) of a white insoluble material was filtered off
15. extractionThe aqueous phase was re-extracted with chloroform
16. dry with materialThe combined chloroform phases were dried over anhydrous magnesium sulfate
17. filtrationfiltered
18. customevaporated to a brown oil (about 5 1/2 g.)
19. dissolutionThe brown oil was dissolved in a small volume of methanol at 40° C.
20. additionwater was added until the resulting cloudiness
21. customThe desired product crystallized out in the form of yellow needles which
22. washwere washed with a small amount of a 1:1 mixture of methanol and water, m.p. 127°-128° C

ORD record

ord-179e05cac26240b9b40046ac46df0ec5

Source dataset

uspto-grants-1977_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04052510