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

HRID 520307Notes

Reaction equation

HRID 520307 reaction equation
[O:1]=[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](=[O:11])[N:3]1[CH2:12][CH2:13][C:14]([N:16]1[CH2:20][C:19]([CH3:22])([CH3:21])[CH2:18][CH:17]1C(O)=O)=O.[C:26]([O:34][CH3:35])(=[O:33])[C:27]#[C:28][C:29]([O:31][CH3:32])=[O:30]>CC(OC(C)=O)=O>[O:11]=[C:4]1[C:5]2[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=2)[C:2](=[O:1])[N:3]1[CH2:12][CH2:13][C:14]1[N:16]2[C:17](=[C:27]([C:26]([O:34][CH3:35])=[O:33])[C:28]=1[C:29]([O:31][CH3:32])=[O:30])[CH2:18][C:19]([CH3:22])([CH3:21])[CH2:20]2

Participants

4

Reactant 2

HCID 12980Dimethyl acetylenedicarboxylateHCID 1177774051-(3-(1,3-Dioxoisoindolin-2-yl)propanoyl)-4,4-dimethylpyrrolidine-2-carboxylic acid

Product 1

HCID 117777472dimethyl 5-(2-(1,3-dioxoisoindolin-2-yl)ethyl)-2,2-dimethyl-2,3-dihydro-1H-pyrrolizine-6,7-dicarboxylateYield 48.7%

Reagents, catalysts & solvents 1

HCID 7918Acetic AnhydrideSolvent

Conditions

Temperature
90 °C

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%).

Workup

  1. stirringThe mixture was stirred at 110° C. for 2 h
  2. customUpon reaction completion
  3. concentrationthe mixture was concentrated under reduced pressure
  4. customThe crude was purified by silica gel chromatography (PE/EA=50/1 to 1/1)

Sources & evidence

ORD record
ord-121fb03a64e74fee9b9cee8126ad7ddc
Source dataset
uspto-grants-2016_05
Patent number
US09326985B2

Reaction notes

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