Synthesis
The general procedure for the synthesis of (5-(prop-1-yn-1-yl)pyridin-3-yl)boronic acid from 3-bromo-5-(prop-1-yn-1-yl)pyridine is as follows:
Method G. Step 2: Anhydrous toluene (1.6 mL/mmol, totaling 188 mL) and anhydrous THF (0.4 mL/mmol, totaling 47 mL) were added to a 1000 mL flame-dried flask under nitrogen protection. Triisopropyl borate (32 mL, 141.36 mmol, 1.2 equiv) and 3-bromo-5-(prop-1-yn-1-yl)pyridine (23 g, 117.8 mmol) were then added. The reaction mixture was cooled to -40 °C and then n-butyllithium (2.5 M hexane solution, 56 mL, 141.36 mmol) was slowly added via syringe pump over a period of 1 hour. Stirring was continued by maintaining the temperature at -40 °C for 0.5 h. Subsequently, the mixture was slowly warmed to -20 °C. The reaction was terminated by adding 2N HCl aqueous solution (120 mL). After separation of the organic layer, the pH of the aqueous phase was adjusted to 7 with 5N NaOH solution. a white solid product began to precipitate at a pH close to 7. The solid product was then added to the mixture. Subsequently, solid NaCl was added to the mixture to saturation and extracted three times with THF (150 mL). The THF extracts were combined and the white solid product (18 g, 95% yield) was obtained by vacuum evaporation.
Product characterization data: 1H NMR (CDCl3) δ 8.67 (s, 1H), 8.48 (s, 1H), 8.09 (s, 1H), 2.06 (s, 3H).
References
[1] Patent: WO2006/138264, 2006, A2. Location in patent: Page/Page column 51
[2] Patent: US2012/165347, 2012, A1. Location in patent: Page/Page column 27
[3] Patent: WO2013/190298, 2013, A1. Location in patent: Page/Page column 40; 41
[4] Patent: WO2013/190300, 2013, A1. Location in patent: Page/Page column 27; 28
[5] Patent: WO2011/2407, 2011, A1. Location in patent: Page/Page column 60
