Water → (S)-tert-butyl 2-((2-(4-bromophenyl)-2-oxoethyl)carbamoyl)pyrrolidine-1-carboxylate

https://huagongshe.com/reaction/1963972

Participants

Role	Name	HCID	Charge
Reactant	Water	HCID 962	—
Reactant	1-Hydroxybenzotriazole	HCID 75771	—
Reactant	Diisopropylethylamine	HCID 81531	—
Reactant	1,2-Pyrrolidinedicarboxylic acid, 1-(1,1-dimethylethyl) ester, (2S)-	HCID 85083	—
Reactant	1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride	HCID 2723939	—
Reactant	2-Amino-1-(4-bromophenyl)ethan-1-one hydrochloride	HCID 2798216	—
Solvent	Dichloromethane	HCID 6344	—
Product	(S)-tert-butyl 2-((2-(4-bromophenyl)-2-oxoethyl)carbamoyl)pyrrolidine-1-carboxylate	HCID 56605334	90%

Reaction Steps

A solution of N-Boc-L-Proline (5.16 g, 24.0 mmol) and HOBt.H2O (3.67 g, 24.0 mmol) was stirred at room temperature for 10 min and then treated with N-ethyl-N′-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC.HCl, 4.60 g, 24.0 mmol). The resulting mixture was stirred at room temperature for 30 min and then treated with a yellow solution formed by stirring 2-amino-4′-bromoacetophenone hydrochloride (5.0 g, 20.0 mmol) and N,N-diisopropylethylamine (DIPEA, 2.58 g, 20 mmol) in dichloromethane (DCM, 150 ml) at room temperature for 10 min. The resulting mixture was stirred at room temperature overnight and then filtered through Celite® to remove the precipitate. The filtrate was extracted with DCM and H2O. The organic layer was washed with brine, dried over MgSO4, filtered, and concentrated. The residue was purified with column chromatography (ethyl acetate:hexanes=2:5) to yield pure product 1a as a yellow gel (7.39 g, 90%).

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08415482B2
Source dataset	uspto-grants-2013_04
ORD ID	ord-130b6e45d6a948a8af6d28eb49552e73
Source note	uspto-grants-2013_04