Methylamine → Cis-5-(N-methylcarbamyl)-1-benzylpyrrolidine-2-carboxylic acid
Reaction equation
[CH2:1]([N:8]1[C@H:12]([C:13](O)=[O:14])[CH2:11][CH2:10][C@@H:9]1[C:16]([OH:18])=[O:17])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(OC(=O)C)(=O)C.[CH3:26][NH2:27]>>[CH3:26][NH:27][C:13]([C@H:12]1[N:8]([CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[C@@H:9]([C:16]([OH:18])=[O:17])[CH2:10][CH2:11]1)=[O:14]Participants
Procedure
Cis-N-benzylpyrrolidine-2,5-dicarboxylic acid (41.3 g, 0.166 mole) and acetic anhydride (206.5 ml) were heated carefully together to 100° C; the solid gradually dissolved, and the mixture assumed a dark brown color. In typical experiments, solution was complete in 10-30 minutes, depending on the state of subdivision of the starting material. Heating time was minimized. Just before the last solid dissolved, the excess acetic anhydride was removed in vacuo, and the brown oily residue of crude cis-N-benzylpyrrolidine-2,5-dicarboxylic acid anhydride was taken up in 400 ml benzene. Anhydrous methylamine (0.33 mole as 9.9% solution in benzene) was added in two portions, and the mixture was heated on the steam bath for 45 minutes. After cooling, the crude cis-5-(N-methylcarbamyl)-1-benzylpyrrolidine-2-carboxylic acid (35.8 g) was collected by filtration, washed with benzene and recrystallized from ethanol. Yield: 31.4 g (72%), melting point 190°-192° C.
Workup
- dissolutionthe solid gradually dissolved
- temperatureHeating time
- dissolutionJust before the last solid dissolved
- customthe excess acetic anhydride was removed in vacuo
- temperaturethe mixture was heated on the steam bath for 45 minutes
- temperatureAfter cooling
- filtrationthe crude cis-5-(N-methylcarbamyl)-1-benzylpyrrolidine-2-carboxylic acid (35.8 g) was collected by filtration
- washwashed with benzene
- customrecrystallized from ethanol
Sources & evidence
- ORD record
- ord-6b003eb147ad4ba2b21ca5a7b5913d9c
- Source dataset
- uspto-grants-1976_04
- Patent number
- US03951980
Reaction notes
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