Hydrogen Bromide → HCID 68916741, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of benzyl 3,4-dihydro-7-nitro-2H-pyrano[3,2-b]pyridin-3-ylcarbamate and benzyl 6,8-dihydro-3-nitro-5H-pyrano[3,4-b]pyridine-5-ylcarbamate (6.54 g, 26.23 mmol) in CH2Cl2 (55 ml) was stirred at 0° C. and 33% HBr in acetic acid (45 ml) was added. The solution was further stirred at 0° C. for 1 h then at room temperature for 2 h. The solvents were then removed. The crude mixture was dissolved in CH2Cl2/H2O 1/1 (80 ml) and the aqueous mixture adjusted to pH˜10 with 2N NaOH solution. After separation of the layers, the organic phase was washed with H2O (×2), dried over Na2SO4 and evaporated. The residue was dissolved in CH2Cl2 (400 ml) and the solution cooled to 0° C. Propionyl chloride (4.54 ml, 52 mmol) and triethylamine (7.22 ml, 52 mmol) were added and then the mixture was allowed to reach 20° C. and stirred for 4.5 h. The solution was washed successively with 1 N aqueous HCl, saturated aqueous NaHCO3 and water. The organic layer was dried (Na2SO4) and evaporated. Immediate recrystallization in acetone gave a pure fraction of N-(6,8-dihydro-3-nitro-5H-pyrano[3,4-b]pyridin-5-yl)propionamide (2.2 g, 33% for two steps) as a white solid. The remaining mixture was subjected to chromatography on silica gel (heptane:ethyl acetate, 1.5:3.5 then CH2Cl2:CH3OH, 95:5) to afford another portion of N-(6,8-dihydro-3-nitro-5H-pyrano[3,4-b]pyridin-5-yl)propionamide (1.15 mg, 17% for two steps) and N-(3,4-dihydro-7-nitro-2H-pyrano[3,2-b]pyridin-3-yl)propionamide (445 mg, 7% for two steps) as a white solid.

Provenance & Evidence