Water → tert-Butyl 4-(3-ethoxy-3-oxopropanoyl)piperidine-1-carboxylate

HRID 1801552Notes

Reaction equation

C(O[C:4]([CH:6]1[CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:8][CH2:7]1)=[O:5])C.[C:19]([O:22][CH2:23][CH3:24])(=[O:21])[CH3:20].CC(C)([O-])C.[K+].O>CN(C=O)C>[C:15]([O:14][C:12]([N:9]1[CH2:8][CH2:7][CH:6]([C:4](=[O:5])[CH2:20][C:19]([O:22][CH2:23][CH3:24])=[O:21])[CH2:11][CH2:10]1)=[O:13])([CH3:16])([CH3:17])[CH3:18]

Participants

Conditions

Temperature: 50 °C

Procedure

Piperidine-1,4-dicarboxylic acid 1-tert-butyl ester 4-ethyl ester (0.50 g, 1.94 mmol) in DMF (5 mL) was mixed with ethyl acetate (0.38 mL, 3.88 mmol) and potassium tert-butoxide (0.33 g, 2.92 mmol). The mixture was heated to 50° C. for 20 hours. After cooling to room temperature, water was added (50 mL) and the product was extracted with diethyl ether. The ether extract was dried over sodium sulfate, filtered and concentrated. The crude product was purified by column chromatography on silica gel, eluting with heptane-ethyl acetate to provide 4-(2-ethoxycarbonylacetyl)-piperidine-1-carboxylic acid tert-butyl ester (0.27 g, 47% yield). 1H NMR (300 MHz, CDCl3/TMS): δ=4.20 (q, 2H, J=7.2 Hz), 4.18-4.05 (m, 2H), 3.50 (s, 2H), 2.86-2.70 (m, 2H), 2.68-2.55 (m, 1H), 1.90-1.78 (m, 2H), 1.60-1.50 (m, 2H), 1.45 (s, 9H), 1.28 (t, 3H, J=7.2 Hz). 13C NMR (75 MHz, CDCl3/TMS): 6=204.21, 167.20, 154.67, 79.91, 61.70, 48.93, 47.56, 43.41, 28.73, 27.56, 14.46.

Workup

temperatureAfter cooling to room temperature
extractionthe product was extracted with diethyl ether
extractionThe ether extract
dry with materialwas dried over sodium sulfate
filtrationfiltered
concentrationconcentrated
customThe crude product was purified by column chromatography on silica gel
washeluting with heptane-ethyl acetate

Sources & evidence

ORD record: ord-6085d96d27f74f888a0cda2cda3a2c8f
Source dataset: uspto-grants-2013_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08349833B2

Reaction notes

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