Hydrochloric Acid → HCID 178479535, compound

Participants

Reaction Steps

In a 125 ml, 3-necked round bottom flask equipped with thermometer, condenser, stir bar and heated in an oil bath was added 1.69 g (0.0067 mole) of F, 0.507 g (0.0073 mole, 1.1 equiv.) of hydroxylamine hydrochloride, 0.409 g (0.0073 mole, 1.1 equiv.) of potassium hydroxide and 40 ml of abs. ethanol. This yellow slurry was stirred and heated to reflux for 3 hours, then stirred at room temperature overnight. TLC showed the reaction to be complete, so the slurry was filtered and rinsed with 50 ml of ethanol. The ethanol was evaporated off under vacuum to yield a tan solid. This solid was dissolved in 200 ml of ethyl acetate and washed with 2×100 ml of distilled water, dried over MgSO4, filtered and evaporated to yield 1.92 g of crude product. This crude product was eluted through a silica gel column using 60% EtOAc/hexane. After collecting the fractions and TLCing them, the clean fractions were combined and evaporated to yield 1.7 g of 5-(4-hydroxy-3-trifluoromethylphenyl)-N-hydroxy-2-furancarboximidamide (E1). E1 was dissolved in 50 ml of ether in a 100 ml flask and then acidified with methanolic/HCl to a pH of 1-3. After stirring for a few minutes, a pink solid precipitated. This was filtered and air dried to yield 1.68 g. TLC showed two spots, so the crude product was dissolved in 10 ml of methanol, then the pH was adjusted to basic side with 10% NaHCO3 solution to remove the HCl salt. A white solid precipitated and was filtered and air dried to yield 1.49 g. TLC--Rf =0.45 (10% MeOH/CHCl3) gave one spot. This pure product was dissolved in 50 ml of ether and acidified with methanolic/HCl solution to a pH of 1-3 and a white solid precipitated. This white solid was filtered and air dried to yield 1.4 g of 5-(4-hydroxy-3-trifluoromethylphenyl)-N-hydroxy-2-furancarboximidamide hydrochloride (E2). TLC--Rf =0.27 (10% MeOH/CHCl3). IR and NMR were consistent with a structure of E2.

Provenance & Evidence