2-[2-(4-tert-Butoxycarbonyl-piperazin-1-yl)-1-ethoxy-2-pyridin-2-yl-ethyl]-malonic acid diethyl ester → 1-(4-tert-Butoxycarbonyl-piperazin-1-yl)-4-oxo-1,9a-dihydro-4H-quinolizine-3-carboxylic acid ethyl ester

HRID 1192388Notes

Reaction equation

C([O:3][C:4](=O)[CH:5]([CH:11](OCC)[CH:12]([N:19]1[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:21][CH2:20]1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=1)[C:6]([O:8][CH2:9][CH3:10])=[O:7])C>C1(C)C(C)=CC=CC=1>[CH2:9]([O:8][C:6]([C:5]1[C:4](=[O:3])[N:14]2[CH:13]([CH:18]=[CH:17][CH:16]=[CH:15]2)[CH:12]([N:19]2[CH2:20][CH2:21][N:22]([C:25]([O:27][C:28]([CH3:30])([CH3:29])[CH3:31])=[O:26])[CH2:23][CH2:24]2)[CH:11]=1)=[O:7])[CH3:10]

Participants

Conditions

Temperature: 140 °C

Procedure

2-[2-(4-tert-Butoxycarbonyl-piperazin-1-yl)-1-ethoxy-2-pyridin-2-yl-ethyl]-malonic acid diethyl ester (2.40 g, 4.86 mmol) was dissolved in xylene (20 mL) and heated at 140° C. for 12 hours. After cooling, the volatiles were evaporated and the residue was purified by column chromatography (EtOAc) to give 1-(4-tert-Butoxycarbonyl-piperazin-1-yl)-4-oxo-1,9a-dihydro-4H-quinolizine-3-carboxylic acid ethyl ester (1.39 g, 71%) as an orange solid. 1H NMR (CDCl3, 400 MHz) δ 9.48 (d, J=7.2 Hz, 1H), 8.34 (s, 1H), 7.69 (td, J=7.2 Hz, J=1.2 Hz, 1H), 7.23 (m, 1H), 4.44 (q, J=7.2 Hz, 2H), 4.14 (m, 2H), 3.10 (m, 2H), 2.88 (m, 4H), 1.51 (s, 9H), 1.43 (t, J=7.2 Hz, 3H). LCMS (APCI+) m/z 402 [M+H]+; Rt=2.85 min.

Workup

temperatureAfter cooling
customthe volatiles were evaporated
customthe residue was purified by column chromatography (EtOAc)

Sources & evidence

ORD record: ord-fe2b3039f40a4d89ae4be859cecb4478
Source dataset: uspto-grants-2014_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08680114B2

Reaction notes

Loading…