Sodium Carbonate → HCID 20316405, compound

Participants

Reaction Steps

4,6-Dichloropicolinate was synthesized according to the procedures described in WO 2006/053227. To a solution of the methyl 4,6-dichloropicolinate (2.52 g, 12.2 mmol) in dioxane (100 mL) was added 2-(4-(4-fluorophenoxy)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (3.83 g, 12.2 mmol), 2M aqueous Na2CO3 solution (12.5 mL, 25 mmol) and PdCl2(dppf) (0.502 g, 0.62 mmol). The vessel was heated at reflux under nitrogen overnight. After cooling, the reaction was partitioned between 100 mL EtOAc and 50 mL brine and washed with additional brine. The organics were dried over MgSO4, filtered and concentrated in vacuo. The residue was dissolved in MeOH (150 mL) and concentrated H2SO4 (1.5 mL) was added. The vessel was heated at reflux under nitrogen overnight. After cooling the reaction was quenched by addition of 10 g NaHCO3. The mixture was evaporated in vacuo and the residue partitioned between 100 mL EtOAc and 50 mL brine. The organics were washed once with 50 mL brine. The combined aqueous washes were extracted once with 50 mL EtOAc. The combined organics were dried over MgSO4, filtered and concentrated in vacuo. The residue was chromatographed over silica gel eluting with 5-25% EtOAc in hexanes. The product fractions were isolated and evaporated in vacuo to yield the product methyl 4-chloro-6-(4-(4-fluorophenoxy)phenyl)picolinate as a pale tan oil (1.426 g, 3.99 mmol, 33% yield, LC/MS: m/z=358.1 [M+H]+).

Provenance & Evidence