Electric Literature of 109838-85-9,Some common heterocyclic compound, 109838-85-9, name is (R)-2-Isopropyl-3,6-dimethoxy-2,5-dihydropyrazine, molecular formula is C9H16N2O2, 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.
Step A – Preparation of Compound Int- 13cA 5 L- 3 necked round bottomed flask, equipped with a mechanical stirrer, temperature probe, addition funnel and N2 inlet, was charged with the Schollkopf chiral auxiliary-(Int-13a, 200 g, 1.09 mol, 1.0 eq), bis(chloromethyl) dimethylsilane (Int-13b, 256 g, 1.63 mol, 1.5 eq), and THF (2 L, Aldrich anhydrous). The flask was cooled in a dry ice/ 2- propanol bath until the internal temperature reached -75 ¡ãC. n-Butyllithium (Aldrich 2.5 M in hexanes , 478 mL, 1.19 mol, 1.09 eq) was added via a dropping funnel over 1 hour while maintaining the internal reaction temperature between -67 ¡ãC and -76 ¡ãC. The resulting orange-red solution was allowed to gradually warm to room temperature for about 15 hours. The reaction mixture was then re-cooled to 0 ¡ãC and quenched with 500 mL of water.Diethyl ether (2L) was added and the layers were separated. The aqueous layer was extracted with 1 L of diethyl ether. The combined organic layers was washed with water and brine, dried with MgS04, filtered, and concentrated in vacuo to dryness, giving 480 g of orange oil. This material was left in vacuo for about 15 hours to provide 420 g of oil. The crude product was split into two batches and purified via silica gel chromatography on a 1.6 kg flash column. The column was eluted with gradient of 0-4percent Et20 in hexanes. The product fractions were concentrated in vacuo at a bath temperature at or below 40 ¡ãC giving 190 grams of Int-13c-(60percentyield).
These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route (R)-2-Isopropyl-3,6-dimethoxy-2,5-dihydropyrazine, its application will become more common.
Reference:
Patent; MERCK SHARP & DOHME CORP.; DWYER, Michael P; KEERTIKAR, Kartik M; COBURN, Craig A; WU, Hao; HU, Bin; ZHONG, Bin; ZHANG, Chengren; DAN, Zhigang; WO2012/40924; (2012); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem