Maleic Acid → trans-tert-butyl 5a',6',7',8',9',9a'-hexahydro-5'H-spiro[piperidine-4,4'-pyrrolo[1,2-a]quinoxaline]-1-carboxylate

HRID 1405337Notes

Reaction equation

Cl.[N:2]1([C@@H:7]2[CH2:12][CH2:11][CH2:10][CH2:9][C@H:8]2[NH2:13])[CH:6]=[CH:5][CH:4]=[CH:3]1.O=[C:15]1[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][CH2:16]1.C(O)(=O)/C=C\C(O)=O>C(O)C>[CH:6]1[N:2]2[C@H:7]3[C@H:8]([NH:13][C:15]4([CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][CH2:16]4)[C:3]2=[CH:4][CH:5]=1)[CH2:9][CH2:10][CH2:11][CH2:12]3

Participants

Conditions

Temperature: 80 °C

Procedure

trans-2-(1H-Pyrrol-1-yl)cyclohexanamine hydrogen chloride (989 mg, 4.93 mmol), tert-butyl 4-oxopiperidine-1-carboxylate (982 mg, 4.93 mmol), and maleic acid (56.2 mg, 0.493 mmol) were combined in ethanol (12 mL). The reaction mixture was heated at 80° C. for 4 hours. The reaction mixture was cooled to room temperature and the solvent was evaporated. The residue was dissolved in dichloromethane and was then purified on 80 g of silica gel utilizing a gradient of 0-10% methanol in dichloromethane to give trans-tert-butyl 5a′,6′,7′,8′,9′,9a′-hexahydro-5′H-spiro[piperidine-4,4′-pyrrolo[1,2-a]quinoxaline]-1-carboxylate. ESI-MS m/z calc. 345.2, found 346.2 (M+1)+; Retention time: 1.63 minutes (4 min run).

Workup

temperatureThe reaction mixture was cooled to room temperature
customthe solvent was evaporated
dissolutionThe residue was dissolved in dichloromethane
customwas then purified on 80 g of silica gel utilizing a gradient of 0-10% methanol in dichloromethane

Sources & evidence

ORD record: ord-c3368757f2b146c9bdf88f2748720674
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08916565B2

Reaction notes

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