反应详情

温度

-78 °C

A 5 liter 3-necked round bottom flask is equipped with an overhead mechanical stirrer under nitrogen, the flask is charged with tetrahydrofuran (1 L) and cooled to −78° C. To this stirred solution is added tert-butyllithium (1.7 M in pentane, 800 mL, 1.36 mol) via canula followed by 2-methoxypyridine (132.2 g, 1.21 mol) at −78° C. The mixture is allowed to stir for one hour at −78° C. To the mixture is added N-formyl-N,N′,N′-trimethylethylenediamine (176 mL, 1.37 mol) dropwise at −78° C. described as in Comins, D. L.; Baevsky, M. F.; Hong, H. J. Am. Chem. Soc. 1992, 114, 10972. The reaction mixture is stirred for about 30 min at −78° C. before warming to −23° C. over about 30 min. To the mixture at −23° C. is added ethylene glycol dimethyl ether (1 L) followed by n-butyllithium (2.5 M in hexanes, 800 mL, 2.0 mol). The resultant mixture is stirred for about 2 hours during which time the reaction mixture turns deep green. A 12 liter 4-neck round bottom flask is equipped with an overhead mechanical stirrer under nitrogen, the 12 liter flask is charged with iodine (571 g, 2.25 mol) and ethylene glycol dimethyl ether (2 L) and the resultant solution is cooled to −78° C. The contents of the 5 liter flask are transferred via canula to the mixture of iodine and ethylene glycol dimethyl ether in the 12 liter flask at −78° C. After the addition is complete, the reaction mixture is stirred for an additional 1 hour at −78° C. The cooling bath is removed and the mixture is allowed to warm to about 0° C. then treated with 2 L of water and 2 L of 1N hydrochloric acid. Methyl t-butyl ether (2 L) is added and the layers are separated. The aqueous layer is extracted with 2×1 L of methyl t-butyl ether. The combined organic extracts are washed with 1.2 L of saturated sodium thiosulfate solution followed by 1.2 L of saturated sodium chloride solution. The organic extracts are dried over sodium sulfate, filtered, and concentrated in vacuo to give a thick slurry. To the slurry is added 1 L of hexane resulting in the generation of additional precipitate. The mixture is cooled in an ice/water bath for about 30 min then filtered yielding 4-iodo-2-methoxypyridine-3-carbaldehyde. The filtrate is reconcentrated to a slurry and treated with hexane to generate additional precipitate again yielding 4-iodo-2-methoxypyridine-3-carbaldehyde. Chromatography (silica gel, 10% ethyl acetate/hexane) yields an analytical sample as a bright yellow solid: mp 98-99° C. 1H-NMR (400 MHz, CDCl3) 10.21 (s, 1H), 7.86 (d, J=5 Hz, 1 H), 7.54 (d, J=5 Hz, 1H), 4.06 (s, 3 H); IR (CHCl3) 1710, 1560, 1470, 1380, 1305, 1260, 1025 cm−1; Elemental analysis: calculated for C7H6NO2I: C, 31.97%; H, 2.30; N, 5.32; I, 48.25. Found: C, 32.06; H, 2.35; N, 5.25; I, 48.35.

1. customA 5 liter 3-necked round bottom flask is equipped with an overhead mechanical stirrer under nitrogen
2. stirringThe reaction mixture is stirred for about 30 min at −78° C.
3. temperaturebefore warming to −23° C. over about 30 min
4. customA 12 liter 4-neck round bottom flask is equipped with an overhead mechanical stirrer under nitrogen
5. additionAfter the addition
6. stirringthe reaction mixture is stirred for an additional 1 hour at −78° C
7. customThe cooling bath is removed
8. temperatureto warm to about 0° C.
9. additionthen treated with 2 L of water and 2 L of 1N hydrochloric acid
10. additionMethyl t-butyl ether (2 L) is added
11. customthe layers are separated
12. extractionThe aqueous layer is extracted with 2×1 L of methyl t-butyl ether
13. washThe combined organic extracts are washed with 1.2 L of saturated sodium thiosulfate solution
14. dry with materialThe organic extracts are dried over sodium sulfate
15. filtrationfiltered
16. concentrationconcentrated in vacuo
17. customto give a thick slurry
18. temperatureThe mixture is cooled in an ice/water bath for about 30 min
19. filtrationthen filtered