Hydrochloric Acid → 1-[2-(4-Fluorophenyl)ethyl]-4-ethyl-2,6-dioxopiperidine-3-carbonitrile

HRID 896565Notes

Reaction equation

[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][NH:10][C:11](=[O:16])/[CH:12]=[CH:13]/[CH2:14][CH3:15])=[CH:4][CH:3]=1.[C:17]([CH2:19][C:20]([O:22]CC)=O)#[N:18].CC(C)([O-])C.[K+].O1CCCC1.Cl>C(O)(C)(C)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][CH2:9][N:10]2[C:11](=[O:16])[CH2:12][CH:13]([CH2:14][CH3:15])[CH:19]([C:17]#[N:18])[C:20]2=[O:22])=[CH:6][CH:7]=1

Participants

Conditions

Temperature: 80 °C

Procedure

A solution of trans 2-pentenoic acid [2-(4-fluorophenyl)ethyl]amide (2.0 g, 9.05 mmol) and ethyl cyanoacetate (1.93 mL, 18.1 mmol) in tert-butanol (30 mL) was treated with a solution of potassium tert-butoxide in tetrahydrofuran (1.0 M, 18.1 mL, 18.1 mmol) and heated at 80° C. After 18 hours, the solution was cooled to room temperature and treated with 1.0 N aqueous hydrochloric acid. The mixture was concentrated under vacuum and the residue was recrystallized from ethanol to provide a pale pink solid (2.0 g, 77%). 1H NMR (300 MHz, CDCl3) δ7.19 (m, 2H), 7.00 (t, J=9 Hz, 2H), 4.01 (m, 2H), 3.50 (d, J=11 Hz, 1H), 2.97 (dd, J=17, 3 Hz, 1H), 2.83 (t, J=8 Hz, 2H), 2.4-2.2 (m, 2H), 1.88 (m, 1H), 1.44 (m, 1H), 1.02 (t, J=7 Hz, 3H). Mass spec (ES−) m/z 287.2 (M+H+, 100%).

Workup

temperaturethe solution was cooled to room temperature
concentrationThe mixture was concentrated under vacuum
customthe residue was recrystallized from ethanol

Sources & evidence

ORD record: ord-004f08fbf9bc47379591cefe0a74009e
Source dataset: uspto-grants-2005_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06919356B2

Reaction notes

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