Citric Acid → N-(1-methyl-1-phenylethyl)thiazole-2-carboxamide

HRID 501226Notes

Reaction equation

HRID 501226 reaction equation
[C:1]([NH2:10])([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)([CH3:3])[CH3:2].C[Al](C)C.[S:15]1[CH:19]=[CH:18][N:17]=[C:16]1[C:20](OCC)=[O:21].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C1(C)C=CC=CC=1.O>[CH3:2][C:1]([NH:10][C:20]([C:16]1[S:15][CH:19]=[CH:18][N:17]=1)=[O:21])([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)[CH3:3]

Participants

7

Reactant 4

HCID 311Citric AcidHCID 68509CumylamineHCID 13032471Ethyl 1,3-thiazole-2-carboxylateHCID 16682925Trimethylaluminum

Product 1

HCID 68461307N-(1-methyl-1-phenylethyl)thiazole-2-carboxamideYield 67.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent2×

Procedure

7.13 ml (50.0 mmol) of cumylamine and 156 ml of toluene are placed in a 1-liter three-necked flask with stirring and under an inert atmosphere. 24.8 ml (49.6 mmol) of trimethylaluminium are then added dropwise, and white fumes are evolved. After waiting until the medium has clarified, a solution of 3.9 g (24.8 mmol) of ethyl 2-thiazolecarboxylate (2) in 195 ml of toluene is added. The mixture is stirred for 15 minutes and then refluxed. After heating for 15 hours, the reaction medium is poured into 300 ml of 1M citric acid solution diluted with 200 ml of water and the whole is filtered through Celite®. The Celite® is washed with 100 ml of ethyl acetate and the aqueous phase is extracted with twice 100 ml of ethyl acetate. The organic extracts are combined and dried over magnesium sulfate, and after evaporating under reduced pressure, the residue is purified by flash chromatography (msilica=200 g; eluent: dichloromethane). 4.1 g of N-(1-methyl-1-phenylethyl)thiazole-2-carboxamide are obtained in the form of a brick-red solid. Rf(dichloromethane)=0.4.

Workup

  1. waitAfter waiting until the medium
  2. stirringThe mixture is stirred for 15 minutes
  3. temperaturerefluxed
  4. temperatureAfter heating for 15 hours
  5. filtrationthe whole is filtered through Celite®
  6. washThe Celite® is washed with 100 ml of ethyl acetate
  7. extractionthe aqueous phase is extracted with twice 100 ml of ethyl acetate
  8. dry with materialdried over magnesium sulfate
  9. customafter evaporating under reduced pressure
  10. customthe residue is purified by flash chromatography (msilica=200 g; eluent: dichloromethane)

Sources & evidence

ORD record
ord-b1ffc2ff5b0c4a938b7ab4e5ce39413d
Source dataset
uspto-grants-2010_08
Patent number
US07772261B2

Reaction notes

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