Ethyl chloroacetate → 2-(4-Trifluoromethyl-phenyl)-thiazole-5-carboxylic acid ethyl ester

HRID 1393075Notes

Reaction equation

HRID 1393075 reaction equation
[CH3:1][CH2:2][O-].[Na+].[CH:5]([O:7][CH2:8][CH3:9])=[O:6].C(OC(=O)CCl)C.[F:17][C:18]([F:29])([F:28])[C:19]1[CH:24]=[CH:23][C:22]([C:25](=[S:27])[NH2:26])=[CH:21][CH:20]=1>CCOCC>[CH2:8]([O:7][C:5]([C:1]1[S:27][C:25]([C:22]2[CH:23]=[CH:24][C:19]([C:18]([F:28])([F:17])[F:29])=[CH:20][CH:21]=2)=[N:26][CH:2]=1)=[O:6])[CH3:9]

Participants

6

Reactant 4

HCID 7751Ethyl chloroacetateHCID 8025Ethyl formateHCID 2723922Sodium ethoxideHCID 27348234-(Trifluoromethyl)thiobenzamide

Product 1

HCID 210512492-(4-Trifluoromethyl-phenyl)-thiazole-5-carboxylic acid ethyl esterYield 71%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

To a solution of NaOEt (21% in EtOH, 215 ml, 584 mmol) were added ethyl formate (46.97 ml, 584 mmol) and then, with cooling (max. 28° C.), chloro acetic acid ethyl ester in Et2O (200 ml). The mixture was stirred at RT for 20 h and filtered after adding Et2O (200 ml). The resulting solid was dissolved in EtOH (400 ml) and after addition of 4-(trifluoromethyl)benzene-1-carbothioamide (11.98 g, 58.4 mmol) stirring to reflux was accomplished for 20 h. After filtration, the EtOH was removed under reduced pressure and extracted with CH2Cl2 (3×)/H2O. The organic phases were washed with H2O, dried (Na2SO4) and evaporated to give crude compound which was crystallized (Et2O/n-pentane) to give 12.43 g (71%) of 2-(4-trifluoromethyl-phenyl)-thiazole-5-carboxylic acid ethyl ester as off-white crystals, MS: 301 (M+), MP: 98-110° C.

Workup

  1. filtrationfiltered
  2. additionafter adding Et2O (200 ml)
  3. dissolutionThe resulting solid was dissolved in EtOH (400 ml)
  4. stirringstirring
  5. temperatureto reflux
  6. waitwas accomplished for 20 h
  7. filtrationAfter filtration
  8. customthe EtOH was removed under reduced pressure
  9. extractionextracted with CH2Cl2 (3×)/H2O
  10. washThe organic phases were washed with H2O
  11. dry with materialdried (Na2SO4)
  12. customevaporated
  13. customto give crude compound which
  14. customwas crystallized (Et2O/n-pentane)

Sources & evidence

ORD record
ord-53caa0b945ce46649b2e4b00e33e50ec
Source dataset
uspto-grants-2008_03
Patent number
US07345067B2

Reaction notes

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