Synthesis
The general procedure for the synthesis of 2-hydroxymethylpyrazine from methyl pyrazine-2-carboxylate was as follows: methyl pyrazine-2-carboxylate (8.5 g) was dissolved in water (200 mL), sodium borohydride (11.65 g) was added, and the reaction mixture was stirred. A vigorous exothermic phenomenon was observed during the addition. After continuing to stir vigorously for 30 minutes, ethanol (80 mL) and saturated potassium carbonate solution (150 mL) were added sequentially. The mixture was continued to be stirred for 30 minutes and subsequently extracted with ethyl acetate (5 x 150 mL) and dichloromethane (5 x 150 mL). The organic phases were combined, dried and concentrated to give pyrazin-2-ylmethanol as a yellow oil (5.43 g, 80% yield), which could be used in the next reaction without further purification. The NMR hydrogen spectrum (DMSO-D6) data of the product were as follows: δ 4.65 (s, 2H), 5.57 (br s, 1H), 8.54 (d, 2H), 8.71 (s, 1H).
References
[1] Journal of Organic Chemistry, 2018, vol. 83, # 3, p. 1431 - 1440
[2] Patent: WO2004/93880, 2004, A1. Location in patent: Page/Page column 86
[3] Patent: WO2017/214359, 2017, A1. Location in patent: Page/Page column 73
[4] Synthetic Communications, 2005, vol. 35, # 24, p. 3187 - 3190
[5] Patent: US2011/237584, 2011, A1. Location in patent: Page/Page column 132
