Methanol → Methyl pyrazinoate

Thionyl chloride (0.146 L, 1998 mmol) was added to methanol (1.5 L) dropwise at −5° to 0° C. over a period of 1 hour and was stirred at this temperature for 30 minutes. The solution was allowed to warm to room temperature whereupon 2-pyrazine carboxylic acid (62 g, 500 mmol) was added. The mixture was cautiously heated at reflux for 6 h and allowed to cool to room temperature overnight. LCMS indicated that the reaction was complete. The solvents were removed in vacuo and the residue was partitioned between ethyl acetate (500 mL) and saturated sodium bicarbonate solution (500 mL). The aqueous phase was extracted with ethyl acetate (3×500 mL), the combined organic extracts were washed with water (250 mL), brine (250 mL), dried over anhydrous sodium sulfate and concentrated in vacuo to afford a crude solid. The solid was recrystalised from ˜500 ml of 1:1 pentane:cyclohexane, decanting the hot solution twice off a dark viscous oil. Care was taken to minimise the amount of product oiling out upon cooling affording as cream needles. The mothor liquors were concentrated in vacuo and the residue recrystalised from the same solvent (˜200 mL) affording a second crop, as buff needles. Analysis by LCMS and NMR indicates that both materials are consistant with desired product and of comaparable purity. Both batches were combined to afford product in 42.8 g as beige needles.

1. additionwas added
2. temperatureThe mixture was cautiously heated
3. temperatureat reflux for 6 h
4. customThe solvents were removed in vacuo
5. customthe residue was partitioned between ethyl acetate (500 mL) and saturated sodium bicarbonate solution (500 mL)
6. extractionThe aqueous phase was extracted with ethyl acetate (3×500 mL)
7. washthe combined organic extracts were washed with water (250 mL), brine (250 mL)
8. dry with materialdried over anhydrous sodium sulfate
9. concentrationconcentrated in vacuo
10. customto afford a crude solid
11. customThe solid was recrystalised from ˜500 ml of 1:1 pentane
12. customcyclohexane, decanting the hot solution twice off a dark viscous oil
13. temperatureupon cooling
14. customaffording as cream needles
15. concentrationThe mothor liquors were concentrated in vacuo
16. customthe residue recrystalised from the same solvent (˜200 mL)
17. customaffording a second crop

ORD record

ord-e91ae6f7ff9848e093af8e5dc7bc77c4

Source dataset

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08501946B2