2-[2-(3-Methyl-4-chloro-pyridin-2-yl)-2-cyclopropyl-ethylidene]-malonic acid diethyl ester → ethyl 8-chloro-1-cyclopropyl-9-methyl-4-oxo-4H-quinolizine-3-carboxylate

HRID 1854824Notes

Reaction equation

HRID 1854824 reaction equation
[CH2:1]([O:3][C:4](=[O:24])[C:5](=[CH:11][CH:12]([C:16]1[C:21]([CH3:22])=[C:20]([Cl:23])[CH:19]=[CH:18][N:17]=1)[CH:13]1[CH2:15][CH2:14]1)[C:6](OCC)=[O:7])[CH3:2]>C1C=CC(C2C=CC=CC=2)=CC=1.C1C=CC(OC2C=CC=CC=2)=CC=1>[Cl:23][C:20]1[CH:19]=[CH:18][N:17]2[C:16]([C:21]=1[CH3:22])=[C:12]([CH:13]1[CH2:15][CH2:14]1)[CH:11]=[C:5]([C:4]([O:3][CH2:1][CH3:2])=[O:24])[C:6]2=[O:7]

Participants

3

Reactant 1

HCID 669802852-[2-(3-Methyl-4-chloro-pyridin-2-yl)-2-cyclopropyl-ethylidene]-malonic acid diethyl ester

Product 1

HCID 12071709ethyl 8-chloro-1-cyclopropyl-9-methyl-4-oxo-4H-quinolizine-3-carboxylateYield 75%

Reagents, catalysts & solvents 1

HCID 246701,1'-Biphenyl, mixt. with 1,1'-oxybis(benzene)Solvent

Procedure

A solution of 2-[2-(3-methyl-4-chloro-pyridin-2-yl)-2-cyclopropyl-ethylidene]-malonic acid diethyl ester (5.76 g, 16.4 mmol) in Dowtherm A (80 mL) was heated in a preheated oil bath at 230° C. for 15 min. The reaction mixture was cooled to room temperature and purified by flash silica column chromatography (hexane:ethyl acetate, 2:1 to 1:2) to afford the title compound as a yellow solid (3.76 g, 75%). ESI-MS m/z: 306 (M+H)+; 1H NMR (CDCl3, 300 MHz) δ ppm: 9.34 (d, J=7.8 Hz, 1H), 8.40 (s, 1H), 7.12 (d, J=7.8 Hz, 1H), 4.41 (q, 2H), 3.00 (s, 3H), 2.28-2.33 (m, 1H), 1.42 (t, 3H), 1.03-1.08 (m, 2H), 0.71-0.76 (m, 2H).

Workup

  1. custompurified by flash silica column chromatography (hexane:ethyl acetate, 2:1 to 1:2)

Sources & evidence

ORD record
ord-d168123a88934eb59776d8f7aaf176bd
Source dataset
uspto-grants-2015_02
Patent number
US08962842B2

Reaction notes

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