反应详情

To a solution of 2-chloro-4-methyl-5-nitropyridine (Aldrich Chemical Co.) (5.0 g, 29.0 mmol) in concentrated sulfuric acid (60 mL) with stirring at 0° C., was added a solution of sodium dichromate dihydrate (14.3 g, 1.65 eq) in concentrated sulfuric acid (100 mL) at a rate which kept the internal temperature less than 10° C. After addition was complete, the reaction mixture was stirred from 0° C. to room temperature over 6 hours. By TLC, the reaction was not complete, so additional sodium dichromate dihydrate (8.4 g, 1 eq) was added directly to the solution at 0° C. The resulting solution was stirred from 0° C. to room temperature overnight. The reaction was complete by TLC the next morning, and it was poured into a mixture of ice (1 L) and EtOAc (900 mL). The resulting mixture was stirred for about 10 minutes and then the layers were separated. The organic layer was washed with brine (2×600 mL), and the EtOAc layer was dried over magnesium sulfate and filtered. With stirring at room temperature, trimethylsilyl diazomethathane (2.0M in hexanes, 15 mL) was added to the EtOAc filtrate. The resulting mixture was stirred at room temperature for 30 min. By TLC, there was no acid remaining, and then MeOH (150 mL) was added and the solution stirred for 30 minutes. The solution was concentrated and then EtOAc (700 mL) was added to the residue which was dried over magnesium sulfate, filtered, concentrated and pumped to give the title compound (1A) as an off-white powder (5.79 g, M+=216, M.P.=60.5–64.1° C.).

1. customthe internal temperature less than 10° C
2. additionAfter addition
3. stirringThe resulting solution was stirred from 0° C. to room temperature overnight
4. stirringThe resulting mixture was stirred for about 10 minutes
5. customthe layers were separated
6. washThe organic layer was washed with brine (2×600 mL)
7. dry with materialthe EtOAc layer was dried over magnesium sulfate
8. filtrationfiltered
9. stirringWith stirring at room temperature
10. additiontrimethylsilyl diazomethathane (2.0M in hexanes, 15 mL) was added to the EtOAc filtrate
11. stirringThe resulting mixture was stirred at room temperature for 30 min
12. additionMeOH (150 mL) was added
13. stirringthe solution stirred for 30 minutes
14. concentrationThe solution was concentrated
15. additionEtOAc (700 mL) was added to the residue which
16. dry with materialwas dried over magnesium sulfate
17. filtrationfiltered
18. concentrationconcentrated