Reaction #607489

Reaction equation

137i

1-(3-(1,3-dioxoisoindolin-2-yl)propanoyl)-4,4-dimethylpyrrolidine-2-carboxylic acid

dimethyl but-2-ynedioate

→

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

Yield 48.7%

Solvents

Ac2O

Conditions

Workup

1. 1
   workup.STIRRINGThe mixture was stirred at 110° C. for 2 h
2. 2
   OtherUpon reaction completion
3. 3
   Concentrationthe mixture was concentrated under reduced pressure
4. 4
   OtherThe crude was purified by silica gel chromatography (PE/EA=50/1 to 1/1)

Procedure

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%).

Source