tert-Butyl bromoacetate → tert-Butyl 3-nitro-2-oxo-1(2H)-pyridineacetate

Participants

Reaction Conditions

Reaction Steps

2-Hydroxy-3-nitro-pyridine (75 g, 0.535 mole) and 1400 mL of anhydrous tetrahydrofuran were stirred at 0° C. using a mechanical stirrer. Lithium bis(trimethylsilyl)amide (1.0 M solution in tetrahydrofuran, 683.5 mL) was slowly added over 30 minutes. The deep brown reaction mixture was stirred for 30 additional minutes and then t-butyl bromoacetate (109.6 g, 0.561 mole) was slowly added over 30 minutes. The reaction mixture was warmed to 25° C. overnight. The organic solvents were removed under vacuum and the residue was dissolved in 2 liters of ethyl acetate and 500 mL of water. The organic phase was dried with magnesium sulfate, filtered and evaporated under vacuum. The residue was chromatographed on silica gel using a methylene chloride:ethanol gradient, 100:0 to 98:2, to yield 102.1 g (75 %) of the title compound as a yellow-orange solid.

Provenance & Evidence