Hydrochloric Acid → Methyl 6-[3-(benzyloxy)-4-chlorophenyl]-5-hydroxypyridine-2-carboxylate

Participants

Reaction Conditions

Reaction Steps

Stir a solution of 37 g (163 mmol) of methyl 6-bromo-5-hydroxy-2-pyridine carboxylate and 51 g (196 mmol) of [3-(benzyloxy)-4-chlorophenyl]boronic acid in 300 mL of anhydrous DMF for 15 min while bubbling with argon, then add 63.8 g (196 mmol) of anhydrous caesium carbonate and 5 g (4.33 mmol) of Pd(PPh3)4. Stir the reaction mixture for 10 h at 90° C. under argon, cool to RT, then distribute in 1 L of ether/EtOAc 1:1 mixture and 1 L of a 0.5N aqueous HCl solution. Extract the aqueous phase again with 500 mL of EtOAc/ether 1:1 mixture. Combine the organic phases and wash with 4×500 mL of water. After drying over Na2SO4 and concentration under reduced pressure, take up the precipitate with 500 mL of a 7:3 mixture of pentane/DCM, filter and wash with pentane. We thus obtain 32 g of methyl 6-[3-(benzyloxy)-4-chlorophenyl]-5-hydroxypyridine-2-carboxylate in the form of yellow ochre powder.

Provenance & Evidence