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

Participants

Role	Name	HCID	Charge
Reactant	Formaldehyde	HCID 712	—
Reactant	Diisopropylethylamine	HCID 81531	—
Reactant	3,3-Dimethylmorpholine hydrochloride	HCID 22342863	—
Reactant	(2R)-[3,5-bis(trifluoromethyl)benzoyl]-2-(3,4-dimethylbenzyl)-4-propargylpiperazine	HCID 53973560	—
Catalyst	Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)	HCID 24350	—
Solvent	1,4-Dioxane	HCID 31275	—
Product	(2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(3,4-dimethylbenzyl)-4-[4-(3,3-dimethylmorpholino)-2-butynyl]piperazine	HCID 54544444	—

Reaction Conditions

Temperature	70 °C

Reaction Steps

A mixture of (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(3,4-dimethylbenzyl)-4-(2-propynyl)piperazine (0.49 g), 3,3-dimethylmorpholine hydrochloride (0.185 g), paraformaldehyde (62 mg), diisopropylethylamine (0.21 ml), and copper (1) iodide (20 mg) in 1,4-dioxane (5 ml) was stirred at 70° C. for 1.5 hours. After removal of the solvent by evaporation, the residue was purified by column chromatography on silica gel using a mixed solvent of dichloromethane and methanol (40:1). The fractions containing the objective compound was collected and evaporated under reduced pressure to give a syrup of (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(3,4-dimethylbenzyl)-4-[4-(3,3-dimethylmorpholino)-2-butynyl]piperazine (0.45 g).

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US06924278B2
Source dataset	uspto-grants-2005_08
ORD ID	ord-6e2168cc59894a8d9dd299507199d71b
Source note	uspto-grants-2005_08