反应详情

To a precooled solution of N,N-diisopropylamine (6.2 mL, 0.044 mol) in diethyl ether (125 mL, dried over molecular seives) was added BuLi (2.5 M in hexanes) (17.8 mL, 0,044 mol) and the resulting solution was stirred at rt. for 15 minutes whereafter di-tert-butylsuccinate (5.35 g, 23 mmol) dissolved in diethyl ether (10 mL, dried over molecular seives) was slowly added. After 30 min at −78° C., 3-formyl-4-methyl-2-(pivaloylamino)-pyridine (4.65 g, 21.0 mmol) dissolved in THF (10 mL, LAB-SCAN C2520, dried over molecular seives) was slowly added, and stirring at this temperature was continued for 30 min. The solution was allowed to warm to rt. and poored into a solution of NH4Cl (sat., aqueous, 100 mL). The aqueous phase was extracted three times with diethylether (3×50 mL) and the organic extracts washed with water (50 mL) and brine (50 mL), dried over MgSO4 and evaporated in vacuo. The crude product was recrystallized from ethyl acetate/hexane to yield the diastereomeric mixture which was used as such after drying in vacuo. The diastereomeric mixture was dissolved in HCl (3M, aqueous, 50 mL) the solution was stirred under reflux for 3.5 h, cooled to rt. and washed with diethyl ether (2×50 mL), neutralised with K2CO3 and again washed with chloroform (3×50 mL). After precipitation upon cooling 1.39 g (37%) of the title compound was obtained (mp >250° C.). 1H NMR (D2O/NaOD): δ 8.25 (d, 4.9 Hz, 1H), 7.71 (s, 1H), 6.84 (d, 4.9 Hz, 1H), 2.36 (s, 2H), 1.05 (s, 3H). 13C NMR (D2O/NaOD): δ 180.30, 171.68, 155.44, 148.84, 146.04, 132.61, 127.08, 117.60, 116.21, 27.22, 16.98. FAB+ MS (m/z): 219.10 (M+H+, calc. for C11H10N2O3+H+ 219.0770).

1. additionwas slowly added
2. additionwas slowly added
3. stirringstirring at this temperature
4. waitwas continued for 30 min
5. temperatureto warm to rt
6. extractionThe aqueous phase was extracted three times with diethylether (3×50 mL)
7. washthe organic extracts washed with water (50 mL) and brine (50 mL)
8. dry with materialdried over MgSO4
9. customevaporated in vacuo
10. customThe crude product was recrystallized from ethyl acetate/hexane
11. customto yield the diastereomeric mixture which
12. customafter drying in vacuo
13. dissolutionThe diastereomeric mixture was dissolved in HCl (3M, aqueous, 50 mL) the solution
14. stirringwas stirred
15. temperatureunder reflux for 3.5 h
16. temperaturecooled to rt
17. washand washed with diethyl ether (2×50 mL)
18. washagain washed with chloroform (3×50 mL)
19. customAfter precipitation
20. temperatureupon cooling 1.39 g (37%) of the title compound
21. customwas obtained (mp >250° C.)