Acetic Acid → 2-(2-Amino-thiazol-5-ylmethylene)-malonic acid diethyl ester

HRID 1789929Notes

Reaction equation

HRID 1789929 reaction equation
[NH2:1][C:2]1[S:3][C:4]([CH:7]=O)=[CH:5][N:6]=1.[C:9]([O:17][CH2:18][CH3:19])(=[O:16])[CH2:10][C:11]([O:13][CH2:14][CH3:15])=[O:12].N1CCCCC1.C(O)(=O)C>C(Cl)Cl.CN(C=O)C.C(O)C.CCOC(C)=O>[CH2:14]([O:13][C:11](=[O:12])[C:10](=[CH:7][C:4]1[S:3][C:2]([NH2:1])=[N:6][CH:5]=1)[C:9]([O:17][CH2:18][CH3:19])=[O:16])[CH3:15]

Participants

9

Reactant 4

HCID 176Acetic AcidHCID 7761Diethyl MalonateHCID 8082PiperidineHCID 27377982-Amino-1,3-thiazole-5-carbaldehyde

Product 1

HCID 544471392-(2-Amino-thiazol-5-ylmethylene)-malonic acid diethyl esterYield 18.2%

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

To a solution of 2-amino-thiazole-5-carbaldehyde (47%; 6 g; 23 mmol) in CH2Cl2 (30 mL) and DMF (30 mL), was added 4A molecular sieves, diethyl malonate (3.5 mL; 23 mmol), piperidine (1.1 mL; 11.5 mmol) and acetic acid (0.7 mL; 11.5 mmol). The reaction mixture was stirred at room temperature for 96 hours. Then EtOAc was added, and the reaction mixture was filtered through celite in order to remove the precipitate formed. EtOAc (500 mL) was added to the filtrate, and the organic phase was washed with NaHCO3 and brine. The organic phase was dried and concentrated to yield 4.9 g of the crude product. Addition of petroleum ether to a solution of the crude product in ethanol followed by filtration afforded 2-(2-amino-thiazol-5-ylmethylene)-malonic acid diethyl ester (1.13 g, 18%).

Workup

  1. filtrationthe reaction mixture was filtered through celite in order
  2. customto remove the precipitate
  3. customformed
  4. washthe organic phase was washed with NaHCO3 and brine
  5. customThe organic phase was dried
  6. concentrationconcentrated
  7. customto yield 4.9 g of the crude product
  8. filtrationfollowed by filtration

Sources & evidence

ORD record
ord-c46d7f258e53470bbb2ffe1789913e62
Source dataset
uspto-grants-2006_07
Patent number
US07071175B1

Reaction notes

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