Formaldehyde → (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-4-[4-((3S)-3-isopropylmorpholino)-2-butynyl]-2-(3,4-dimethylbenzyl)piperazine dihydrochloride

Participants

Reaction Steps

A mixture of (2R)-[3,5-bis(trifluoromethyl)benzoyl]-2-(3,4-dimethylbenzyl)-4-propargylpiperazine (286 mg), (3S)-3-isopropylmorpholine hydrochloride (118 mg) and N,N-diisopropylamine (92 mg) in dioxane (3 ml) was stirred at room temperature. Paraformaldehyde (22 mg) and copper(I) chloride (10 mg) were added and the whole was stirred for 30 minutes and then heated at 80° C. for 4 hours. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure. The obtained residue was purified by column chromatography on silica gel using a mixture of hexane and ethyl acetate (1:1) as eluent. The obtained product was dissolved in ethyl acetate and treated with 4N hydrogen chloride in ethyl acetate to give (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-4-[4-((3S)-3-isopropylmorpholino)-2-butynyl]-2-(3,4-dimethylbenzyl)piperazine dihydrochloride (190 mg).

Provenance & Evidence