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

HRID 1526467Notes

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): δ=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-c0e08b82f54344cab3841d2c6cbcc34c
Source dataset: uspto-grants-2015_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09085585B2

Reaction notes

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