Hydrochloric Acid → (2E)-3-(5-{[(3R)-1-(benzyloxy)-6-oxo-3-piperidinyl]amino}-2-pyrazinyl)-N-hydroxyacrylamide

Participants

Reaction Conditions

Reaction Steps

To a solution of ethyl (2E)-3-(5-{[(3R)-1-(benzyloxy)-6-oxo-3-piperidinyl]amino}-2-pyrazinyl)acrylate (200 mg, 0.50 mmol) in methanol (5 mL) was added hydroxylamine hydrochloride (175 mg, 2.52 mmol) at ambient temperature under nitrogen. After cooling, 1M sodium methanolate in methanol (5 mL) was added dropwise to the mixture over 1 h, the reaction mixture was stirred at 0° C. for 2 hrs and at ambient temperature for 4 hrs. The reaction mixture was adjusted to PH 6.0 with 1 mol/L hydrochloric acid and evaporated in vacuo. The residue was dissolved in ethanol and the precipitate was removed by filtration. The solvent was evaporated in vacuo. The residue was purified by preparative HPLC (CH3CN, 20% NH4HCO3/30%˜90%, gradient) to give (2E)-3-(5-{[(3R)-1-(benzyloxy)-6-oxo-3-piperidinyl]amino}-2-pyrazinyl)-N-hydroxyacrylamide (15 mg, 8%) as a powder.

Provenance & Evidence