Ethyl 2-chloroacetoacetate → Ethyl 2-anilino-4-methyl-1,3-thiazole-5-carboxylate

HRID 917388

Reaction equation

HRID 917388 reaction equation
[C:1]1([NH:7][C:8]([NH2:10])=[S:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl[CH:12]([C:18](=O)[CH3:19])[C:13]([O:15][CH2:16][CH3:17])=[O:14]>C(O)C>[CH3:19][C:18]1[N:10]=[C:8]([NH:7][C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[S:9][C:12]=1[C:13]([O:15][CH2:16][CH3:17])=[O:14]

Participants

4

Reactant 2

HCID 11858Ethyl 2-chloroacetoacetateHCID 676454Phenylthiourea

Product 1

HCID 807772Ethyl 2-anilino-4-methyl-1,3-thiazole-5-carboxylateYield 91.5%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To 70 ml of ethanol, 10.7 g (70 mmol) of phenylthiourea and 11.6 g (70 mmol) of ethyl 2-chloro-3-oxobutanate were dissolved, followed by heating under refluxing for 8 hours. The reaction liquid was concentrated and dissolved in ethyl acetate and the organic layer was washed with an aqueous solution of sodium carbonate, water and a saturated saline solution in this order, followed by drying over anhydrous magnesium sulfate and concentrating under reduced pressure. Solid obtained was washed with diisopropyl ether to obtain 16.8 g (yield: 91%) of ethyl 4-methyl-2-(N-phenylamino)thiazole-5-carboxylate. (2) To 50 ml of ethanol, 12.8 g (49 mmol) of ethyl-4-methyl-2-(N-phenylamino)thiazole-5-carboxylate was dissolved, followed by adding 24 g (150 mmol) of 25% sodium hydroxide aqueous solution, and stirring at 80° C. for 15 hours. The reaction liquid was poured into ice water, and acetic acid was added to make acidic. Crystal precipitated was filtered, washed with water and a mixed solvent of hexane/ethyl acetate and dried to obtain 5.50 g (yield: 48%) of 4-methyl-2-(N-phenylamino)thiazole-5-carboxylic acid.

Workup

  1. temperatureby heating
  2. temperatureunder refluxing for 8 hours
  3. customThe reaction liquid
  4. concentrationwas concentrated
  5. dissolutiondissolved in ethyl acetate
  6. washthe organic layer was washed with an aqueous solution of sodium carbonate, water
  7. dry with materialby drying over anhydrous magnesium sulfate
  8. concentrationconcentrating under reduced pressure
  9. customSolid obtained
  10. washwas washed with diisopropyl ether

Sources & evidence

ORD record
ord-6f9ad1ae7dd8467e9631e333a8a5a164
Source dataset
uspto-grants-2007_09
Patent number
US07273878B2

Linked notes

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