Diisopropylethylamine → 2-[2-(4-Bromo-phenyl)-2-oxo-ethylcarbamoyl]-4-cyano-pyrrolidine-1-carboxylic acid tert-butyl ester

https://huagongshe.com/reaction/2039296

Participants

Role	Name	HCID	Charge
Reactant	Diisopropylethylamine	HCID 81531	—
Reactant	2-Amino-1-(4-bromophenyl)ethan-1-one hydrochloride	HCID 2798216	—
Reactant	Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)	HCID 9886157	—
Reactant	(2S,4S)-1-(tert-Butoxycarbonyl)-4-cyano-2-pyrrolidinecarboxylic acid	HCID 14842640	—
Solvent	Dimethylformamide	HCID 6228	—
Solvent	Ethyl Acetate	HCID 8857	—
Product	2-[2-(4-Bromo-phenyl)-2-oxo-ethylcarbamoyl]-4-cyano-pyrrolidine-1-carboxylic acid tert-butyl ester	HCID 66621386	91%

Reaction Conditions

Temperature	0 °C

Reaction Steps

2-Amino-1-(4-bromo-phenyl)-ethanone HCl salt (664 mg, 2.65 mmol) was dissolved in DMF (10 mL) and to this solution was added 4-Cyano-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester crude from the previous step, diisopropyl ethylamine (0.93 mL, 5.3 mmol), followed by HATU (1 g, 2.65 mmol). Reaction mixture was stirred at 0° C. for 30 minutes. The reaction mixture was dissolved in ethyl acetate and washed with dilute sodium bicarbonate solution. The organic layer was dried (MgSO4), concentrated and purified by flash column chromatography (silica gel, 20 to 80% ethyl acetate/hexane) to give 2-[2-(4-Bromo-phenyl)-2-oxo-ethylcarbamoyl]-4-cyano-pyrrolidine-1-carboxylic acid tert-butyl ester (1.05 g, yield 91%).

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08575118B2
Source dataset	uspto-grants-2013_11
ORD ID	ord-0b139e962911488f9fba54cec9fe84de
Source note	uspto-grants-2013_11