Ethyl 2-chloroacetoacetate → Ethyl 2-(4-chloro-2-methoxyphenyl)-4-methylthiazole-5-carboxylate

HRID 1498904Notes

Reaction equation

HRID 1498904 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([NH2:8])=[S:7])=[C:4]([O:11][CH3:12])[CH:3]=1.Cl[CH:14]([C:20]([CH3:22])=O)[C:15]([O:17][CH2:18][CH3:19])=[O:16]>C(O)C>[Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]2[S:7][C:14]([C:15]([O:17][CH2:18][CH3:19])=[O:16])=[C:20]([CH3:22])[N:8]=2)=[C:4]([O:11][CH3:12])[CH:3]=1

Participants

4

Reactant 2

HCID 11858Ethyl 2-chloroacetoacetateHCID 630943604-Chloro-2-methoxythiobenzamide

Product 1

HCID 68642456Ethyl 2-(4-chloro-2-methoxyphenyl)-4-methylthiazole-5-carboxylateYield 78%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

In ethanol (50 ml), 4-chloro-2-methoxythiobenzamide (4.00 g, 20.0 mmol) prepared in the Step 7-1-2 was suspended, and ethyl 2-chloroacetoacetate (3.62 g, 22.0 mmol) was added to the suspension. The mixture was heated under reflux overnight. After the mixture was allowed to cool, the solvent was distilled off under a reduced pressure, and ethyl acetate and a saturated sodium bicarbonate solution were added to the mixture. The resulting mixture was subjected to extraction with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and then concentrated. The residue was suspended in ethyl acetate-n-hexane (ethyl acetate:n-hexane=1:1) and separated by filtration. The separated product was washed with the same solvent and dried under a reduced pressure to give the title compound (4.84 g, 78%) as a light-yellow powder.

Workup

  1. temperatureThe mixture was heated
  2. temperatureunder reflux overnight
  3. temperatureto cool
  4. distillationthe solvent was distilled off under a reduced pressure, and ethyl acetate
  5. additiona saturated sodium bicarbonate solution were added to the mixture
  6. extractionThe resulting mixture was subjected to extraction with ethyl acetate
  7. dry with materialThe extract was dried over anhydrous magnesium sulfate
  8. concentrationconcentrated
  9. customseparated by filtration
  10. washThe separated product was washed with the same solvent
  11. customdried under a reduced pressure

Sources & evidence

ORD record
ord-251f90f270f1410c91b51b6d8826f443
Source dataset
uspto-grants-2015_12
Patent number
US09200008B2

Reaction notes

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