Potassium Carbonate → Methyl 5-(difluoromethoxy)picolinate

Participants

Reaction Conditions

Reaction Steps

A mixture of methyl 5-hydroxypicolinate hydrochloride from step K1 (1.12 g, 5.91 mmol), potassium carbonate (8.16 g, 59.1 mmol) and α-chloro-α,α-difluoroacetophenone (3.92 mL, 26.6 mmol) in water (20 mL) and acetonitrile (20 mL) was stirred at 75° C. for 5 h. The solid was filtered out and washed with diethyl ether. The filtrate was washed with water and concentrated. The residue was purified using silica gel column chromatography (hexanes-50% EtOAc) to give methyl 5-(difluoromethoxy)picolinate (730 mg, 3.59 mmol, 61% yield). 1H NMR (500 HMz, chloroform-d) δ 8.60 (d, J=2.4 Hz, 1H), 8.20 (dd, J=8.6, 0.5 Hz, 1H), 7.62 (dd, J=8.7, 2.7 Hz, 1H), 6.81-6.49 (m, 1H), 4.03 (s, 3H).

Provenance & Evidence