3-(2-bromoacetyl)benzoic Acid → 4-(3-Carboxyacetyl-phenyl)-thiazole-2-carboxylic acid ethyl ester

HRID 1266780Notes

Reaction equation

HRID 1266780 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[S:7][CH:8]=[C:9]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([C:17](Cl)=[O:18])[CH:12]=2)[N:10]=1)=[O:5])[CH3:2].Br[CH2:21][C:22]([C:24]1[CH:25]=[C:26]([CH:30]=[CH:31][CH:32]=1)[C:27]([OH:29])=[O:28])=O.C(OCC)(=S)C(N)=O>C1COCC1>[CH2:1]([O:3][C:4]([C:6]1[S:7][CH:8]=[C:9]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([C:17](=[O:18])[CH2:26][C:27]([OH:29])=[O:28])[CH:12]=2)[N:10]=1)=[O:5])[CH3:2].[CH2:1]([O:3][C:4]([C:6]1[S:7][CH:21]=[C:22]([C:24]2[CH:32]=[CH:31][CH:30]=[C:26]([C:27]([OH:29])=[O:28])[CH:25]=2)[N:10]=1)=[O:5])[CH3:2]

Participants

6

Reactant 3

HCID 27568353-(2-bromoacetyl)benzoic AcidHCID 216137632-ethoxy-2-thioxoAcetamideHCID 865869654-(3-Chlorocarbonyl-phenyl)-thiazole-2-carboxylic acid ethyl ester

Product 2

HCID 697808034-(3-Carboxyacetyl-phenyl)-thiazole-2-carboxylic acid ethyl esterHCID 697810514-(3-Carboxy-phenyl)-thiazole-2-carboxylic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

The 4-(3-carboxyacetyl-phenyl)-thiazole-2-carboxylic acid ethyl ester was prepared from 4-(3-chlorocarbonyl-phenyl)-thiazole-2-carboxylic acid ethyl ester [prepared by the following sequence: i.) A mixture of 3-(2-bromo-acetyl)-benzoic acid [CAS-no. 62423-73-8] (2.43 g) and ethyl thiooxamate [CAS-no. 16982-21-1] (1.6 g) in THF (40 mL) was heated to 60° C. for 4 h and then partitioned between EtOAc and brine. The organic layer was dried and evaporated and the residue was crystallized from EtOAc/hexane to give 4-(3-carboxy-phenyl)-thiazole-2-carboxylic acid ethyl ester (2.2 g) as off-white crystals, mp 225-228° C. ii.) This carboxylic acid (2.1 g) was heated with thionyl chloride in toluene and the resulting carboxylic acid chloride was used directly in the next step.] (2.24 g) and bis(trimethylsilyl)malonate with n-BuLi in ether at −60° C. to 0° C. according to general procedure K (method c2). The crude material was transformed into the title compound by stirring in isopropenyl acetate and conc. H2SO4 according to general procedure L (method a). Obtained as yellow oil (2.7 g).

Workup

  1. customprepared by the following sequence
  2. custompartitioned between EtOAc and brine
  3. customThe organic layer was dried
  4. customevaporated
  5. customthe residue was crystallized from EtOAc/hexane

Sources & evidence

ORD record
ord-a7b9dea0ca6f41308d72dee6aceaf3ba
Source dataset
uspto-grants-2003_04
Patent number
US06548495B2

Reaction notes

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