Sodium Carbonate → Methyl 5-amino-6-[3-(benzyloxy)-4-chlorophenyl]pyrazine-2-carboxylate

Participants

Reaction Steps

Stir a suspension of 137 mg (0.36 mmol) of (bis-benzonitrile)-palladium II dichloride and 183 mg (0.43 mmol) of diphenylphosphinobutane in 7 mL of toluene under argon for 30 min at room temperature. Then add, while bubbling with argon, 1.66 g (7.15 mmol) of methyl 5-amino-6-bromopyrazine-2-carboxylate, 1.97 g (7.51 mmol) of [3-(benzyloxy)-4-chlorophenyl]boronic acid, 2.4 mL of ethanol and 3.58 mL (7.15 mmol) of a 2N aqueous solution of sodium carbonate. Reflux the reaction mixture for 5 h 30 min and then distribute in 100 mL of a water/EtOAc 1:1 mixture. Wash the organic phase with 50 mL of water, dry over Na2SO4 and concentrate under reduced pressure. Purify the residue, obtained by silica gel column chromatography, eluting with a cyclohexane/EtOAc gradient from 50 to 100% of EtOAc. After concentration under reduced pressure, we obtain 1.33 g of methyl 5-amino-6-[3-(benzyloxy)-4-chlorophenyl]pyrazine-2-carboxylate in the form of yellow wax.

Provenance & Evidence