Iodine → Tert-butyl 2-(4-(5-hydroxypicolinoyl)phenoxy)ethyl(methyl)carbamate

Participants

Reaction Conditions

Reaction Steps

Mg (3.5 eq) was added to a 3-neck round bottom flask containing 50 mL anhydrous THF. The mixture was heated to 55° C. Iodine chips (2 grains) were added in one lot followed by addition of 0.1 mL ethyl bromide. Tert-butyl 2-(4-bromophenoxy)ethyl(methyl)carbamate (3.0 eq) was dissolved in 30 mL anhydrous THF, 3 mL of this solution was added at once to Mg-THF suspension. The reaction was initiated after 30 min and reflux started. The remaining solution of tert-butyl 2-(4-bromophenoxy)ethyl(methyl)carbamate was added dropwise in such speed that the reaction mixture remained reflux. After addition, the reaction mixture was further reflux for 2 h and cooled to rt. 5-Hydroxy-N-methoxy-N-methylpicolinamide (1.0 eq) in 20 mL THF was added dropwise at rt, stirred for 30 min. at rt., quenched with sat NH4Cl (aq), and extracted with EtOAc. The extract was dried, concentrated, and purified by column chromatography to give the desired product.

Provenance & Evidence