Triethylamine → N-(4-Carboxybenzyl)cinnamamide

HRID 1111296Notes

Reaction equation

HRID 1111296 reaction equation
C(N1C=CN=C1)(N1C=CN=C1)=O.[C:13]([OH:23])(=O)[CH:14]=[CH:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.Cl.[NH2:25][CH2:26][C:27]1[CH:36]=[CH:35][C:30]([C:31]([O:33]C)=[O:32])=[CH:29][CH:28]=1.C(N(CC)CC)C>O1CCCC1>[C:31]([C:30]1[CH:35]=[CH:36][C:27]([CH2:26][NH:25][C:13](=[O:23])[CH:14]=[CH:15][C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=2)=[CH:28][CH:29]=1)([OH:33])=[O:32]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 87842-Propenoic acid, 3-phenyl-HCID 682631,1'-CarbonyldiimidazoleHCID 2729253Methyl 4-(aminomethyl)benzoate hydrochloride

Product 1

HCID 54481087N-(4-Carboxybenzyl)cinnamamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

1,1'-Carbonyldiimidazole (3.71 g) is added to an ice-cold stirred solution of cinnamic acid (3.13 g) in 30 mL tetrahydrofuran. After stirring for an additional 1 hr, methyl 4-(aminomethyl)benzoate hydrochloride (4.7 g) and triethylamine (3.23 mL) are added and the final mixture stirred while immersed in an ice water bath for an additional 30 min, followed by stirring overnight at room temperature. After removal of the solvent by rotary evaporation, the residue is taken up in chloroform (250 mL) and extracted with water (200 mL), 1N HCl (3×50 mL), water (100 mL), saturated sodium bicarbonate (100 mL), brine (100 mL) and the final chloroform layer dried over anhydrous magnesium sulfate. After evaporation of the solvent in vacuo, the crude product (2.74 g) is suspended in 100 mL tetrahydrofuran and 20 mL 2N NaOH and the mixture stirred at room temperature overnight. The mixture is then made acidic by addition of excess 1N HCl, and the precipitate recovered by filtration. After washing the filter cake with water and pressing to remove as much water as possible, the white solid is crystallized from methanol/2N HCl as N-(4-carboxybenzyl)cinnamamide, m.p. 238°-239° C.

Workup

  1. waitwhile immersed in an ice water bath for an additional 30 min
  2. stirringby stirring overnight at room temperature
  3. customAfter removal of the solvent
  4. customby rotary evaporation
  5. extractionextracted with water (200 mL), 1N HCl (3×50 mL), water (100 mL), saturated sodium bicarbonate (100 mL), brine (100 mL)
  6. dry with materialthe final chloroform layer dried over anhydrous magnesium sulfate
  7. customAfter evaporation of the solvent in vacuo
  8. stirring20 mL 2N NaOH and the mixture stirred at room temperature overnight
  9. additionmade acidic by addition of excess 1N HCl
  10. filtrationthe precipitate recovered by filtration
  11. washAfter washing the filter cake with water
  12. customto remove as much water as possible, the white solid
  13. customis crystallized from methanol/2N HCl as N-(4-carboxybenzyl)cinnamamide, m.p. 238°-239° C.

Sources & evidence

ORD record
ord-5726725bc3054bfc85c037f7d887914c
Source dataset
uspto-grants-1990_12
Patent number
US04980095

Reaction notes

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