These common heterocyclic compound, 6164-79-0, name is Methyl 2-pyrazinecarboxylate, 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. Application In Synthesis of Methyl 2-pyrazinecarboxylate
Procedure: ¡¤ Charged ST-601 (1 kg), NaH, 60 wt.% (579 g) and toluene (10 vol) and stirred at 15/25 C. No reaction (no gas evolution, exotherm or appearance change). (0157) ? Charged methyl propionate (64 g). No immediate reaction (no gas evolution, exotherm or appearance change) at 15/25 C. ? Charged MeOH (85 g) at 15/25 C. Immediately started to react (gas evolution, exotherm). Heated to 30/40 C. (0158) ? Charged methyl propionate (893 g) at 30/40 C over 5 h. The reaction was slower in the beginning, but became faster (more exotherm and gas evolution) after 1-2 h when -0.3 eq of methyl propionate was charged. Stirred at 30/40 C for 88 h. (0159) 64 h, 30/35 C, brown slurry, practically no gas evolution observed, IPC HPLCl: 74.4% + 14.1 % = 88.5% o/ ST-602 at 4.81 min and 5.62 min; 1.2% of ST -601 at 1.97 min; 5.8% of “Int” at 3.21 min. (0160) 72 h, 35 C, IPC HPLC2: 47.8% + 42.9%c=90 % o/ST-602; 0.9% ofST-601; 4.3% of “Int” 88 h, 38 C, IPC HPLC3: 60.3% + 32.6%=92.9% o/ST-602; 0.64% ofST-601; 1.8% of “Int” (0161) ? Reaction was cooled to 15/20 C. (0162) ? Charged AcOH (2.5 eq) over a minimum of 1 hr. Exothermic. Slightly thick, brown suspension. (0163) ? Charged 10% NaCl solution (8 vol) over a minimum of 1 h at 15/30 C. Slight exotherm. Brown, biphasic solution. Let stir at 15/30 C for a minimum of 30 min to dissolve all solids. (0164) ? The phases were separated. Both the aqueous and the organic phases were brown. (0165) ? The organic phase was washed with a 10% NaCl solution (5 vol). (0166) ? The organic phase was washed with NaHC03 (0.1 g/g SM) in 10% aq. NaCl solution (5 vol.) (0167) ? The organic phase was dried over anhydrous sodium sulfate (0.2 g/g SM) for a minimum of 2 hrs. (0168) ? Solids were filtered off and rinsed with Toluene (l x l vol) (0169) ? Concentrated to 3-4 vol at (0170) Isolated material: ST- 602 (0171) Lot No.: 2463-52-2 (0172) Appearance: light brown liquid (0173) Yield: Assumed 100% (1406 g net directly used in next step) HPLC: 94.3% of ST-602
The synthetic route of Methyl 2-pyrazinecarboxylate has been constantly updated, and we look forward to future research findings.
Reference:
Patent; ST IP HOLDING AG; FRAMROZE, Bomi P.; (65 pag.)WO2016/207914; (2016); A2;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem