Application of 75907-74-3, A common heterocyclic compound, 75907-74-3, name is (3,5,6-Trimethylpyrazin-2-yl)methanol, molecular formula is C8H12N2O, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.
Take Ligustrazine 2ยท 176g (16mmol) dissolved into 20ml glacial acetic acid, add 1.8ml (16mmol) of 30% hydrogen peroxide at 90 C for 4h, and then supplement 1.8ml (16mmol) 30% hydrogen peroxide to continue the reaction for 2h, TLC monitoring reaction is complete, add an appropriate amount of sodium sulfite to neutralize excess hydrogen peroxide, the reaction solution was filtered, and the filtrate was cooled at room temperature, adjust the pH at 10 with 50% sodium hydroxide, extract with dichloromethane, collect the organic layer, dehydrate the saturated brine, dry over anhydrous sodium sulfate, and recover the solvent under reduced pressure, obtained white Ligustrazine mono-nitroxide compound crude (2). The crude product is added into 1.51ml (16mmol) of acetic anhydride, heating at 105 C for 2.5 h, after TLC was monitored until the reaction has completed, it was evaporated to get dryness under reduced pressure, obtained black slurry of ligustrazine acetylate (3). The next black slurry was placed in a solution of 20 ml (THF: Me0H: H20 = 3:1:1), add 1.92g (48mmol) sodium hydroxide in batches, the reaction was stirred for 2 h, extracted with dichloromethane and organic layer was collected, dehydrated with saturated brine, dried over anhydrous sodium sulfate, filtered, the solvent is recovered under reduced pressure and then obtained a crude hydroxyl Ligustrazine, that is re-crystallized from n-hexane, obtained 1.85g of yellow needle crystals (4), the yellow crystal of TMP-0H prepared in the previous step was dissolved into 20 ml of anhydrous tetrahydrofuran, after that add 3.03 g (15.9mmol) Tscl, 2.464 g (24.4mmol) TEA, 0.15 g (12.2mmol) DMAP, stir overnight, extract with methylene chloride, dehydrate the saturated brine, dry over anhydrous sodium sulfate, filter, recover solvent, obtained light yellow chloro-Ligustrazine crude product, appropriate amount of silica gel sample, separation on silica gel column [V (petroleum ether): V (ethyl acetate) = 10:1] and then obtained colorless and transparent chloro- Ligustrazine 1.86g, yield 90.3%.
The synthetic route of 75907-74-3 has been constantly updated, and we look forward to future research findings.
Reference:
Patent; Lei Pengcheng; Xu Bing; Wang Penglong; (31 pag.)CN108456239; (2018); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem