Trifluoroacetic acid → HCID 21473526, compound

Participants

Reaction Steps

1-(4-Hydroxy-2-methoxyphenyl)piperazine dihydrobromide (1.95 g, 5.27 mmol) was dissolved in 10 mL of THF and 10 mL of saturated sodium bicarbonate solution and then di(tert-butyl)pyrocarbonate (1.35 g, 6.2 mmol) was added. The mixture was stirred vigorously at room temperature for 18 hours and extracted with diethyl ether (3×25 mL). The combined extracts were washed with brine, dried (MgSO4) and filtered. The solvents were removed in vacuo and the residue was dissolved in 20 mL of DMF. The solution was treated with cesium carbonate (1.46 g, 4.5 mmol) and then benzyl bromide (1.1 g, 4.6 mmol) and stirred at room temperature under nitrogen for 3 hours. The mixture was partitioned between 50 mL of water and 50 mL of diethyl ether. The aqueous layer was separated and extracted with diethyl ether (2×50 mL). The combined diethyl ether was washed with brine, dried (MgSO4), filtered and concentrated. The residue was purified on silica gel by column chromatography eluting with hexanes/ethyl acetate (3:1) to give a pale yellow oil. The oil was dissolved in 20 mL of methylene chloride and the solution was treated with 10 mL of trifluoroacetic acid. After 45 minutes at room temperature the mixture was partitioned between 100 mL of 5M aqueous potassium carbonate and 100 mL of methylene chloride. The aqueous layer was separated and extracted with methylene chloride (2×100 mL). The combined methylene chloride was washed with brine, dried (Na2SO4), filtered and concentrated to give 1-(4-benzyloxy-2-methoxyphenyl)piperazine (1.39 g, 4.7 mmol).

Provenance & Evidence