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

HRID 1854823Notes

Reaction equation

HRID 1854823 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%). ESI-MS m/z: 352 (M+H)+.

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-5c9692f3d3e94919a5b854c63030c234
Source dataset
uspto-grants-2015_02
Patent number
US08962842B2

Reaction notes

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