Ethyl 3-(2,4-dichlorophenyl)-3-oxopropanoate → Ethyl 2-amino-4-(4-chlorophenyl)thiazole-5-carboxylate

HRID 1660564

Reaction equation

HRID 1660564 reaction equation
Cl[C:2]1[CH:15]=[C:14]([Cl:16])[CH:13]=[CH:12][C:3]=1[C:4]([CH2:6][C:7]([O:9][CH2:10][CH3:11])=[O:8])=O.[NH2:17][C:18]([NH2:20])=[S:19]>C(O)C>[NH2:20][C:18]1[S:19][C:6]([C:7]([O:9][CH2:10][CH3:11])=[O:8])=[C:4]([C:3]2[CH:12]=[CH:13][C:14]([Cl:16])=[CH:15][CH:2]=2)[N:17]=1

Participants

4

Reactant 2

HCID 542007Ethyl 3-(2,4-dichlorophenyl)-3-oxopropanoateHCID 2723790Thiourea

Product 1

HCID 12801681Ethyl 2-amino-4-(4-chlorophenyl)thiazole-5-carboxylateYield 80%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a cold (5° C.) vigorously stirred mixture of 121.87 g (0.936 mole) of ethyl acetoacetate, 314 ml. of benzene and 626 ml. of water was added 41.25 ml. of 33% sodium hydroxide. To the above mixture was added simultaneously, in two dropping funnels, 177.0 g (1.01 mole) of p-chlorobenzoyl chloride and 188.8 ml. of 33% sodium hydroxide in 2 hours. The reaction mixture became pasty. The reaction mixture was heated at 35° C. for 1 hour, cooled and filtered to give 170.0 g of sodium salt of ethyl 2-benzoylacetoacetate. Part (150 g) of this salt was added to a mixture of 39.0 g (0.729 mole) of ammonium chloride and 78 ml. of concentrated ammonium hydroxide in 780 ml. of water. The mixture was stirred at 40°-50° C. for 3 hours and cooled in an ice bath. The precipitate was filtered to give 115.5 g of yellow solid which was Kugelrohr distilled to give 76.0 g (38% based on ethyl acetoacetate) of crude ethyl p-chlorobenzoylacetate. A mixture of 40.0 g (0.175 mole) of crude ethyl p-chlorobenzoylacetate, 24.2 g (0.18 mole) of sulfuryl chloride and some chloroform was held at reflux for 6 hours, cooled and concentrated to give 49.0 g of crude ethyl 2-chloro-p-chlorobenzoylacetate. A mixture of 46.0 g (0.174 mole) of crude ethyl 2-chloro-p-chlorobenzoylacetate, 13.25 g (0.174 mole) of thiourea, and 174 ml. of ethanol was held at reflux for 2 hours and cooled. The precipitate was filtered and neutralized with saturated sodium bicarbonate. The insoluble material was filtered to give 37.0 g (80%) of ethyl 2-amino-4-p-chlorophenyl-5-thiazolecarboxylate, m.p. 198°-200° C.

Workup

  1. temperatureat reflux for 2 hours
  2. temperaturecooled
  3. filtrationThe precipitate was filtered
  4. filtrationThe insoluble material was filtered

Sources & evidence

ORD record
ord-8e24eb2258c04df09ce5a2650ea891e0
Source dataset
uspto-grants-1981_12
Patent number
US04308391

Linked notes

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