Itaconic acid → (R)-1-((R)-1-(4-methoxyphenyl)ethyl)-5-oxopyrrolidine-3-carboxylic acid
Reaction equation
[C:1]([OH:9])(=[O:8])[C:2]([CH2:4][C:5]([OH:7])=O)=[CH2:3].[CH3:10][O:11][C:12]1[CH:17]=[CH:16][C:15]([C@H:18]([NH2:20])[CH3:19])=[CH:14][CH:13]=1.O>CN1C(=O)CCC1>[CH3:10][O:11][C:12]1[CH:17]=[CH:16][C:15]([C@H:18]([N:20]2[C:5](=[O:7])[CH2:4][C@@H:2]([C:1]([OH:9])=[O:8])[CH2:3]2)[CH3:19])=[CH:14][CH:13]=1Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 80 °C
Procedure
To a stirred solution of itaconic acid (35 g, 269 mmol) in NMP at 70° C. was added (R)-1-(4-methoxyphenyl)ethanamine (37 g, 245 mmol) via syringe. The mixture was heated at 80° C. for 1 hour and warmed to 120° C. for an additional 4 hours. The reaction was cooled to rt and poured into 550 mL of water with vigorous stirring. The mixture was aged for 1 hour over which time a slurry was formed. The solids were collected via filtration and washed with water. The solids were dried and transferred to a flask and recrystallized from iPrOH. Upon cooling and stirring, a thick slurry was obtained which was filtered to afford solids enriched in the major diastereomer. This material was again recrystallized from iPrOH to obtain (R)-1-((R)-1-(4-methoxyphenyl)ethyl)-5-oxopyrrolidine-3-carboxylic acid 1.01.
Workup
- temperaturewarmed to 120° C. for an additional 4 hours
- temperatureThe reaction was cooled to rt
- customa slurry was formed
- filtrationThe solids were collected via filtration
- washwashed with water
- customThe solids were dried
- customtransferred to a flask
- customrecrystallized from iPrOH
- temperatureUpon cooling
- customa thick slurry was obtained which
- filtrationwas filtered
- customto afford solids
- customThis material was again recrystallized from iPrOH
Sources & evidence
- ORD record
- ord-410186fb96e24952b26005d9e91bf4a6
- Source dataset
- uspto-grants-2016_06
- Patent number
- US09376441B2
Reaction notes
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