反応 #478498

反応方程式

methyl 5-bromonicotinate

ethynyltrimethylsilane

potassium carbonate

→

5-Ethynyl-nicotinic acid methyl ester

溶媒

反応条件

後処理

1. 1
   温度The reaction was cooled to room temperature
2. 2
   ろ過filtered
3. 3
   その他to remove the solids
4. 4
   洗浄The precipitate was washed thoroughly with ethyl acetate
5. 5
   洗浄The filtrate was then washed with water twice
6. 6
   抽出extracted with ethyl acetate
7. 7
   乾燥The organic layer was dried over sodium sulfate
8. 8
   濃縮concentrated in vacuo
9. 9
   その他to afford a black color solid
10. 10
    その他this was taken on to next step for TMS removal
11. 11
    workup.DISSOLUTIONThe crude was dissolved in MeOH (50 mL)
12. 12
    workup.STIRRINGThe reaction mixture was stirred for 30 min
13. 13
    ろ過The solids were filtered off
14. 14
    濃縮the filtrate was concentrated in vacuo
15. 15
    その他The crude was purified by silica gel flash chromatography

実験手順

To methyl 5-bromonicotinate (3.0 g, 13.89 mmol) in TEA (50 mL) under N2 was added ethynyltrimethylsilane (5.83 mL, 41.7 mmol), copper(I) iodide (0.132 g, 0.694 mmol) and bis(triphenylphosphine)palladium(II) chloride (0.487 g, 0.694 mmol). The reaction was stirred at 50° C. for 1 h. The reaction was cooled to room temperature and filtered to remove the solids. The precipitate was washed thoroughly with ethyl acetate. The filtrate was then washed with water twice and extracted with ethyl acetate. The organic layer was dried over sodium sulfate and concentrated in vacuo to afford a black color solid. Assuming 100% conversion this was taken on to next step for TMS removal. The crude was dissolved in MeOH (50 mL) and potassium carbonate (0.480 g, 3.47 mmol) was added to it. The reaction mixture was stirred for 30 min. The solids were filtered off, the filtrate was concentrated in vacuo. The crude was purified by silica gel flash chromatography using DCM-MeOH: 90-10 to give pure product 5-Ethynyl-nicotinic acid methyl ester as a light yellow solid. ESI-MS: m/z 162.1 (M+H)+

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