Acetic Acid → 2-[2-(3-Methyl-4-chloro-pyridin-2-yl)-2-cyclopropyl-ethylidene]-malonic acid diethyl ester

HRID 1478296Notes

Reaction equation

HRID 1478296 reaction equation
[CH3:1][C:2]1[C:3]([CH:9]([CH:12]2[CH2:14][CH2:13]2)[CH:10]=O)=[N:4][CH:5]=[CH:6][C:7]=1[Cl:8].[C:15]([O:23][CH2:24][CH3:25])(=[O:22])[CH2:16][C:17]([O:19][CH2:20][CH3:21])=[O:18].N1CCCCC1.C(O)(=O)C>C(O)C>[CH2:20]([O:19][C:17](=[O:18])[C:16](=[CH:10][CH:9]([C:3]1[C:2]([CH3:1])=[C:7]([Cl:8])[CH:6]=[CH:5][N:4]=1)[CH:12]1[CH2:14][CH2:13]1)[C:15]([O:23][CH2:24][CH3:25])=[O:22])[CH3:21]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 7761Diethyl MalonateHCID 8082PiperidineHCID 186293552-(3-Methyl-4-chloro-pyridin-2-yl)-2-cyclopropyl-acetaldehyde

Product 1

HCID 669802852-[2-(3-Methyl-4-chloro-pyridin-2-yl)-2-cyclopropyl-ethylidene]-malonic acid diethyl esterYield 71.2%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of (3-methyl-4-chloro-pyridin-2-yl)-cyclopropyl-acetaldehyde (4.83 g, 23.0 mmol), diethyl malonate (7.02 g, 43.8 mmol), piperidine (3.62 mL, 36.6 mmol), and acetic acid (4.19 mL, 73.2 mmol) in ethanol (100 mL) was heated to reflux overnight. The reaction mixture was concentrated to dryness. The residue was purified by flash silica column chromatography (hexane:ethyl acetate, 4:1) to afford the title compound as a yellow oil (5.76 g, 71%).

Workup

  1. temperaturewas heated
  2. temperatureto reflux overnight
  3. concentrationThe reaction mixture was concentrated to dryness
  4. customThe residue was purified by flash silica column chromatography (hexane:ethyl acetate, 4:1)

Sources & evidence

ORD record
ord-cbf1a9fd92ac460aba440df92220d24f
Source dataset
uspto-grants-2016_08
Patent number
US09403818B2

Reaction notes

Loading…