Crotononitrile → [1-(2-Cyano-1-methyl-ethyl)-piperidin-4-yl]-carbamic acid tert-butyl ester

HRID 1257611Notes

Reaction equation

[C:1](#[N:5])/[CH:2]=[CH:3]/[CH3:4].[C:6]([O:10][C:11](=[O:19])[NH:12][CH:13]1[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]1)([CH3:9])([CH3:8])[CH3:7]>C(N(CC)CC)C.C(O)C>[C:6]([O:10][C:11](=[O:19])[NH:12][CH:13]1[CH2:18][CH2:17][N:16]([CH:3]([CH3:4])[CH2:2][C:1]#[N:5])[CH2:15][CH2:14]1)([CH3:9])([CH3:7])[CH3:8]

Participants

Conditions

Temperature: 60 °C

Procedure

(E)-but-2-enenitrile (4.5 ml, 55.0 mmol) and triethylamine (2 drops) were added sequentially to a solution of piperidin-4-yl-carbamic acid tert-butyl ester (10 g, 50.0 mmol) in ethanol (120 ml) at 25° C. The reaction mixture was stirred at 60° C. for 1 week, then was cooled to 25° C. and concentrated under reduced pressure to afford crude [1-(2-cyano-1-methyl-ethyl)-piperidin-4-yl]-carbamic acid tert-butyl ester as tan oil. 1H NMR (400 MHz, CDCl3) δ 4.48 (s, 1H), 3.42 (s, 1H), 3.09-2.95 (m, 1H), 2.81-2.61 (m, 3H), 2.49 (dd, J=16.7, 6.0 Hz, 2H), 2.39-2.23 (m, 3H), 1.94 (d, J=11.6 Hz, 2H), 1.44 (s, 9H), 1.18 (d, J=6.7 Hz, 3H). This material was used in the next step below without additional purification or characterization.

Workup

temperaturewas cooled to 25° C.
concentrationconcentrated under reduced pressure

Sources & evidence

ORD record: ord-71268c16ff484b948e5baecf046df9e3
Source dataset: uspto-grants-2013_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08461328B2

Reaction notes

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