Diisopropylamine → 1-tert-Butyl 4,4-diethyl piperidine-1,4,4-tricarboxylate

HRID 1013489Notes

Reaction equation

N(C(C)C)C(C)C.C([Li])CCC.[N:13]1([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:18][CH2:17][CH:16]([C:19]([O:21][CH2:22][CH3:23])=[O:20])[CH2:15][CH2:14]1.Cl[C:32]([O:34][CH2:35][CH3:36])=[O:33]>C1COCC1.Cl>[N:13]1([C:24]([O:26][C:27]([CH3:29])([CH3:28])[CH3:30])=[O:25])[CH2:14][CH2:15][C:16]([C:32]([O:34][CH2:35][CH3:36])=[O:33])([C:19]([O:21][CH2:22][CH3:23])=[O:20])[CH2:17][CH2:18]1

Participants

Conditions

Temperature: -78 °C

Procedure

To a solution of iPr2NH (4.72 g, 46.6 mmol) at −20° C. in THF (70 mL) was added n-butyllithium (13.99 mL, 35.0 mml, 2.5 M in hexanes). After 15 minutes at −20° C., the solution was cooled to −78° C., and 1-tert-butyl 4-ethyl piperidine-1,4-dicarboxylate (6.00 g, 23.3 mmol) was added. After stirring at −78° C. for 1 h, ethyl chloroformate (7.59 g, 70.0 mmol) was added dropwise. The reaction was then allowed to warm to room temperature over 4 h. The solution was diluted with 1 N HCl and extracted with EtOAc (2×). The combined organic extracts were washed with brine, dried (MgSO4), and evaporated. Flash chromatography of the crude (0-25% EtOAc/hexanes) yielded the desired product as a yellow oil. 1H NMR (CDCl3, 600 MHz) δ 4.18 (q, J=7.1 Hz, 4H), 3.43-3.38 (m, 4H), 2.05-2.00 (m, 4H), 1.42 (s, 9H), 1.23 (t, J=7.0 Hz, 6H). MS: cal'd 352 (MNa+), exp 352 (MNa+).

Workup

temperatureto warm to room temperature over 4 h
extractionextracted with EtOAc (2×)
washThe combined organic extracts were washed with brine
dry with materialdried (MgSO4)
customevaporated

Sources & evidence

ORD record: ord-7e844345ba26404dace60ac130c5271c
Source dataset: uspto-grants-2011_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07981874B2

Reaction notes

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