Dimethyl acetylenedicarboxylate → dimethyl 5-(2-(1,3-dioxoisoindolin-2-yl)ethyl)-2,2-dimethyl-2,3-dihydro-1H-pyrrolizine-6,7-dicarboxylate

https://huagongshe.com/reaction/520307

Participants

Role	Name	HCID	Charge
Reactant	Dimethyl acetylenedicarboxylate	HCID 12980	—
Reactant	1-(3-(1,3-Dioxoisoindolin-2-yl)propanoyl)-4,4-dimethylpyrrolidine-2-carboxylic acid	HCID 117777405	—
Solvent	Acetic Anhydride	HCID 7918	—
Product	dimethyl 5-(2-(1,3-dioxoisoindolin-2-yl)ethyl)-2,2-dimethyl-2,3-dihydro-1H-pyrrolizine-6,7-dicarboxylate	HCID 117777472	48.7%

Reaction Conditions

Temperature	90 °C

Reaction Steps

A mixture of 137i (crude, 72.5 mmol) and Ac2O (100 mL) was stirred at 90° C. for 0.5 h. Then dimethyl but-2-ynedioate 137j (20.6 g, 145 mmol) was added. See FIG. 2. The mixture was stirred at 110° C. for 2 h. Upon reaction completion, the mixture was concentrated under reduced pressure. The crude was purified by silica gel chromatography (PE/EA=50/1 to 1/1) to give dimethyl 5-(2-(1,3-dioxoisoindolin-2-yl)ethyl)-2,2-dimethyl-2,3-dihydro-1H-pyrrolizine-6,7-dicarboxylate 137k (15 g, 48%).

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US09326985B2
Source dataset	uspto-grants-2016_05
ORD ID	ord-121fb03a64e74fee9b9cee8126ad7ddc
Source note	uspto-grants-2016_05