Pyridine → 2-(1-Ethyl-propylidene)-malonic acid dimethyl ester

HRID 1806936Notes

Reaction equation

HRID 1806936 reaction equation
[C:1]([O:8][CH3:9])(=[O:7])[CH2:2][C:3]([O:5][CH3:6])=[O:4].[CH3:10][CH2:11][C:12](=O)[CH2:13][CH3:14].N1C=CC=CC=1.ClCCl>O1CCCC1.Cl[Ti](Cl)(Cl)Cl.O>[CH3:6][O:5][C:3](=[O:4])[C:2](=[C:12]([CH2:13][CH3:14])[CH2:11][CH3:10])[C:1]([O:8][CH3:9])=[O:7]

Participants

8

Reactant 4

HCID 1049PyridineHCID 6344DichloromethaneHCID 7288Ethyl ketoneHCID 7943Dimethyl malonate

Product 1

HCID 856487702-(1-Ethyl-propylidene)-malonic acid dimethyl esterYield 46.6%

Reagents, catalysts & solvents 3

HCID 24193Titanium TetrachlorideCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Step A To a solution of dimethyl malonate (10 g, 75 mmol), 3-pentanone (6.5 g, 75 mmol) and pyridine (7.9 g, 100 mmol) in anhydrous tetrahydrofuran (300 mL) at 0° C. was added a dichloromethane solution (1 M) of TiCl4 (100 mL, 100 mmol) during a period of 1 h. After the addition was finished, the reaction mixture was gradually warmed room temperature and stirred for 18 h. Water was added to quench the reaction. The mixture was extracted with ethyl ether. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate. The organic layers were combined, concentrated. The residue was purified by chromatography (EtOAc:hexanes=1:20) to give 2-(1-ethyl-propylidene)-malonic acid dimethyl ester as a light yellow oil (7 g, 46%).

Workup

  1. additionAfter the addition
  2. customwas gradually warmed room temperature
  3. customto quench
  4. customthe reaction
  5. extractionThe mixture was extracted with ethyl ether
  6. customThe organic layer was separated
  7. extractionthe aqueous layer was extracted with ethyl acetate
  8. concentrationconcentrated
  9. customThe residue was purified by chromatography (EtOAc:hexanes=1:20)

Sources & evidence

ORD record
ord-b3bda9c158c3401ab88cb01c0c8f55b5
Source dataset
uspto-grants-2013_01
Patent number
US08354444B2

Reaction notes

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