tert-Butyl 4-oxopiperidine-1-carboxylate → Tert-butyl 4-oxo-3-(2-phenylpropanoyl)piperidine-1-carboxylate

HRID 1930640Notes

Reaction equation

[O:1]=[C:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[C:25]1([CH:31]([CH3:35])[C:32](Cl)=[O:33])[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1>C1(C)C=CC=CC=1.C1COCC1>[O:1]=[C:2]1[CH2:3][CH2:4][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:6][CH:7]1[C:32](=[O:33])[CH:31]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[CH3:35]

Participants

Conditions

Temperature: 0 °C

Procedure

tert-Butyl 4-oxopiperidine-1-carboxylate (2.363 g, 11.86 mmol) was dissolved in toluene (7 mL) and cooled to 0° C. LHMDS (12.45 mL, 12.45 mmol) in THF was added. After 2 min 2-phenylpropanoyl chloride (0.855 mL, 5.93 mmol) was added. After 2 min the cooling bath was removed and after 5 min 1:1 acetic acid:water (3 ml) was added. The water phase was separated after hard stirring and the organic phase was dried with MgSO4 and the solvent was evaporated. Purification by flash column chromatography (0-25% EtOAc in heptane) yielded tert-butyl 4-oxo-3-(2-phenylpropanoyl)piperidine-1-carboxylate (1.319 g, 67.1%). MS (ES−) m/z 330.1 (M−H)−

Workup

customAfter 2 min the cooling bath was removed and after 5 min 1:1 acetic acid
additionwater (3 ml) was added
customThe water phase was separated
dry with materialthe organic phase was dried with MgSO4
customthe solvent was evaporated
customPurification by flash column chromatography (0-25% EtOAc in heptane)

Sources & evidence

ORD record: ord-348dec5f2b8b4069bf42aaa5ee8892e9
Source dataset: uspto-grants-2012_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08188101B2

Reaction notes

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