Citric Acid → 1,1-Dimethylethyl 3,3-dimethyl-2-oxo-1-piperidinecarboxylate

HRID 1457219Notes

Reaction equation

O=[C:2]1CCCC[N:3]1[C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9].C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[CH3:25]I.C(O)(=O)[CH2:28][C:29]([CH2:34][C:35](O)=O)([C:31]([OH:33])=O)O>C1COCC1.CCOCC>[CH3:25][C:29]1([CH3:28])[CH2:34][CH2:35][CH2:2][N:3]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[C:31]1=[O:33]

Participants

Conditions

Temperature: -78 °C

Procedure

To the title compound of Step (A) (1.08 g, 5.42 mmol) in 10.8 ml THF at -78° C., lithium bis(trimethylsilyl)amide (1M in THF, 13.6 ml, 13.6 mmol) was added dropwise in 10 min. The mixture was stirred at -78° C. for 30 minutes and methyl iodide (4.62 g, 32.52 mmol) was added. The reaction mixture was slowly warmed to room temperature and stirred at room temperature for two days. To the reaction mixture, 30 ml Et2O and 15 ml 5% aqueous citric acid were added. The organic liquid was separated and washed with 10 ml 5% citric acid, H2O, brine and dried and concentrated. The residue was chromatographed on silica gel using 19:1 hexane/EtOAc to give the title compound of this step (440 mg, 38%) as a light yellow oil.

Workup

temperatureThe reaction mixture was slowly warmed to room temperature
stirringstirred at room temperature for two days
customThe organic liquid was separated
washwashed with 10 ml 5% citric acid, H2O, brine
customdried
concentrationconcentrated
customThe residue was chromatographed on silica gel using 19:1 hexane/EtOAc

Sources & evidence

ORD record: ord-408b8951bf974325b04a01a5404ac5ea
Source dataset: uspto-grants-1998_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05846990

Reaction notes

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