Dichloromethane → HCID 73554912, compound

Participants

Reaction Conditions

Reaction Steps

Methyl 6-chloro-3-methoxypicolinate (prepared as in Van Heertum, J. C. et al. U.S. Pat. No. 5,571,775 A, Nov. 5, 1996; 4.0 g, 20 mmol) was dissolved in dry CH2Cl2 (20 mL), treated with urea hydrogen peroxide complex (4.0 g, 43 mmol), cooled to 0-5° C., stirred and treated in portions with trifluoroacetic anhydride (5.6 mL, 40 mmol). The mixture was allowed to warm to 20° C. and stirred for 20 h. An additional portion of the urea hydrogen peroxide complex (2.0 g) and trifluoroacetic anhydride (2.8 mL) were added and stirring was continued for 4 h. The mixture was stirred with 10% sodium bisulfite (NaHSO3) solution until negative to starch-iodide paper. The organic phase was washed with H2O (10 mL), dried (Na2SO4) and evaporated. This material was dissolved in phosphorus oxychloride (POCl3; 30 mL) and heated at 70° C. for 2 h and then at reflux for 3 h to produce a 1:1 mixture of the isomeric 4,5- and 4,6-dichloropicolinates. After cooling, the volatiles were removed under vacuum, the residue was combined with ice and the product was taken up in EtOAc. This solution was washed with H2O, dried (Na2SO4) and evaporated. The crude mixture was purified by reverse-phase high performance liquid chromatography (RP-HPLC; eluting with 60% acetonitrile (CH3CN)—H2O) to provide the title compound (1.1 g, 23%): 1H NMR (400 MHz, CDCl3) δ 7.50 (s, 1H), 3.99 (s, 3H), 3.98 (s, 3H); EIMS m/z 235.

Provenance & Evidence