Formic Acid → Methyl 5-methoxy-3-methylpyrazine-2-carboxylate

HRID 627693Notes

Reaction equation

Cl[C:2]1[N:7]=[C:6]([C:8]([O:10][CH3:11])=[O:9])[C:5]([CH3:12])=[N:4][C:3]=1[O:13][CH3:14].C(N(CC)CC)C.C(O)=O>[Pd].CC(C)=O>[CH3:14][O:13][C:3]1[N:4]=[C:5]([CH3:12])[C:6]([C:8]([O:10][CH3:11])=[O:9])=[N:7][CH:2]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To a mixture of methyl 6-chloro-5-methoxy-3-methylpyrazine-2-carboxylate (6.5 g, 30.0 mmol) and palladium, 10% wt. on activated carbon (3.19 g, 3.00 mmol) in a 500 mL flask under nitrogen, was added acetone (200 mL) carefully. The flask was cooled to 0° C. and triethylamine (30 mL, 216 mmol) was added followed by formic acid (96%) (5.66 mL, 150 mmol) dropwise. The suspension was warmed to room temperature with stirring and then heated at 40° C. for 1 h. The reaction mixture was concentrated, diluted with saturated sodium hydrogenocarbonate solution and extracted with DCM. The organic layer was dried and concentrated. The crude product was purified by ISCO column chromatography using 0-20% EtOAc in DCM to give methyl 5-methoxy-3-methylpyrazine-2-carboxylate (5.2 g, 95% yield). 1H NMR (300 MHz, CDCl3) δ ppm 8.11 (1H, s), 4.02 (3H, s), 3.97 (3H, s), 2.80 (3H, s)

Workup

temperatureThe suspension was warmed to room temperature
temperatureheated at 40° C. for 1 h
concentrationThe reaction mixture was concentrated
additiondiluted with saturated sodium hydrogenocarbonate solution
extractionextracted with DCM
customThe organic layer was dried
concentrationconcentrated
customThe crude product was purified by ISCO column chromatography

Sources & evidence

ORD record: ord-143dc49bb9c243cfa8816dbb3a9a9cb3
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09309263B2

Reaction notes

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