1-Hydroxybenzotriazole → (S)-4-[(E)-3-(3-Chloro-4-fluoro-phenyl)-acryloyl]-1-(3-hydroxy-propyl)-3-methyl-piperazin-2-one

Participants

Role	Name	HCID	Charge
Reactant	1-Hydroxybenzotriazole	HCID 75771	—
Reactant	Diisopropylethylamine	HCID 81531	—
Reactant	1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride	HCID 2723939	—
Reactant	3-(3-Chloro-4-fluorophenyl)prop-2-enoic acid	HCID 2773644	—
Reactant	(S)-1-(3-Hydroxy-propyl)-3-methyl-piperazin-2-one	HCID 66999467	—
Solvent	Dimethylformamide	HCID 6228	—
Product	Dichloromethane methanol ammonium hydroxide	HCID 21896990	—
Product	(S)-4-[(E)-3-(3-Chloro-4-fluoro-phenyl)-acryloyl]-1-(3-hydroxy-propyl)-3-methyl-piperazin-2-one	HCID 44541810	168.3%

Reaction Steps

A solution of 3-chloro-4-fluorocinnamic acid (4.52 g, 21.9 mmol), (S)-1-(3-hydroxy-propyl)-3-methyl-piperazin-2-one (3.76 g, 21.9 mmol), N,N-diisopropylethylamine (8.46 g, 65.5 mmol), 1-hydroxybenzotriazole (3.25 g, 24.0 mmol), and N-ethyl-N′-(3-dimethylaminopropyl)carbodiimide hydrochloride (4.60 g, 24.0 mmol) in N,N-dimethylformamide (80 ml) was stirred at room temperature for 18 h, then partitioned between 1 M aq. hydrochloric acid solution and ethyl acetate. The organic layer was washed with 1 M aq. hydrochloric acid solution, sat. aq. sodium hydrogencarbonate solution, and brine, dried (MgSO4), filtered, and evaporated. Chromatography (SiO2; CH2Cl2/MeOH/NH4OH 90:10:0.25) produced the title compound (6.54 g, 84%). Colorless gum, MS (ISP)=355.2 (M+H)+.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08063042B2
Source dataset	uspto-grants-2011_11
ORD ID	ord-66de992757c8403397d08c83cde9234f
Source note	uspto-grants-2011_11