反应详情

温度

-80 °C

To a mixture of THF (100 mL) and hexane (40 mL) under nitrogen atmosphere was added DIPA (22.21 mL, 158.78 mmole, 1.1 eq). The mixture was cooled to −80° C. and to this was added n-BuLi (63.57 mL, 158.78 mmole, 1.1 eq) dropwise. After completion of addition the resulting mixture was allowed to warm and stirred at −10° C. for 15 min. The reaction mixture was again cooled to −80° C. and a solution of 6-chloro-nicotinonitrile (20 g, 144.35 mmol, 1 eq) in THF (100 mL) was added dropwise. The resulting mixture was stirred at −80° C. for 1 h. After 1 h a solution of iodine (43.96 g, 173.22 mmole, 1.2 eq) in THF (100 mL) was added in one portion. After completion of the reaction, the reaction was quenched with water (100 mL) and extracted with diethyl ether (6×100 mL). Combined organic layers were washed with saturated solution of sodium thiosulfate (2×100 mL), dried over sodium sulfate, filtered and concentrated under vacuum to give crude product. Crude compound was purified by column chromatography over silica gel (100-200 mesh) using 2% ethyl acetate-hexane as the eluant to yield the title compound as a faintly yellow solid (15 g, 39%). 1H-NMR (400 MHz, DMSO-d6): δ 8.38 (s, 1H), 8.79 (s, 1H). LC-MS calculated for C6H2ClIN2 (M+H) 264.90. found 264.9.

1. additionwas added DIPA (22.21 mL, 158.78 mmole, 1.1 eq)
2. additionAfter completion of addition the resulting mixture
3. temperatureto warm
4. temperatureThe reaction mixture was again cooled to −80° C.
5. stirringThe resulting mixture was stirred at −80° C. for 1 h
6. customAfter completion of the reaction
7. customthe reaction was quenched with water (100 mL)
8. extractionextracted with diethyl ether (6×100 mL)
9. washCombined organic layers were washed with saturated solution of sodium thiosulfate (2×100 mL)
10. dry with materialdried over sodium sulfate
11. filtrationfiltered
12. concentrationconcentrated under vacuum
13. customto give crude product
14. customCrude compound was purified by column chromatography over silica gel (100-200 mesh)