Water → tert-Butyl 3-ethyl-4-oxopiperidine-1-carboxylate

HRID 242576Notes

Reaction equation

[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11](=[O:14])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].N1CC[CH2:17][CH2:16]1.O.ICC>C1C=CC=CC=1.C1(C)C=CC(S(O)(=O)=O)=CC=1>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][C:11](=[O:14])[CH:12]([CH2:16][CH3:17])[CH2:13]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

Conditions

Temperature: 100 °C

Procedure

A solution of 4-oxo-piperidine-1-carboxylic acid tert-butyl ester (5 g, 25.1 mmol), pyrollidine (5 mL) and p-toluenesulfonic acid (25 mg) in benzene (100 mL) was heated at reflux for 16 h with azeotropic distillation of water. The resulting enamine solution was cooled to rt and concentrated. The crude enamine was dissolved in acetonitrile (50 mL); iodoethane (4.67 g, 30.1 mmol.) was added and the mixture was heated at 100° C. for 0.5 h, cooled to rt and concentrated. The mixture was dissolved in ethyl acetate (200 mL), washed with 1 N hydrochloric acid, saturated aqueous sodium bicarbonate, and brine. The extract was dried over magnesium sulfate, filtered and concentrated. The crude compound was purified by silica gel chromatography (80% hexanes/20% ethyl acetate) to afford 3-ethyl-4-oxo-piperidine-1-carboxylic acid tert-butyl ester (680 mg).

Workup

concentrationconcentrated
dissolutionThe crude enamine was dissolved in acetonitrile (50 mL)
temperaturecooled to rt
concentrationconcentrated
dissolutionThe mixture was dissolved in ethyl acetate (200 mL)
washwashed with 1 N hydrochloric acid, saturated aqueous sodium bicarbonate, and brine
dry with materialThe extract was dried over magnesium sulfate
filtrationfiltered
concentrationconcentrated
customThe crude compound was purified by silica gel chromatography (80% hexanes/20% ethyl acetate)

Sources & evidence

ORD record: ord-30ad9d97f9334e24854b2f6a57f097b1
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08653096B2

Reaction notes

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