Triethylamine → N-(3-Formyl-4-hydroxybenzoyl)phenylalanine methyl ester

HRID 258247Notes

Reaction equation

HRID 258247 reaction equation
C1(N=C=NC2CCCCC2)CCCCC1.[CH:16]([C:18]1[CH:19]=[C:20]([CH:24]=[CH:25][C:26]=1[OH:27])[C:21]([OH:23])=O)=[O:17].ON1C(=O)CCC1=O.Cl.[CH3:37][O:38][C:39](=[O:49])[C@H:40]([CH2:42][C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1)[NH2:41].C(N(CC)CC)C>C(Cl)(Cl)Cl.CN(C)C=O>[CH3:37][O:38][C:39](=[O:49])[C@H:40]([CH2:42][C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1)[NH:41][C:21](=[O:23])[C:20]1[CH:24]=[CH:25][C:26]([OH:27])=[C:18]([CH:16]=[O:17])[CH:19]=1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 10868DicyclohexylcarbodiimideHCID 75736Methyl L-phenylalaninate hydrochlorideHCID 80170N-HydroxysuccinimideHCID 2717613-Formyl-4-hydroxybenzoic acid

Product 1

HCID 53719078N-(3-Formyl-4-hydroxybenzoyl)phenylalanine methyl ester

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
10 °C

Procedure

87 mmol of dicyclohexylcarbodiimide are added to a stirred suspension, cooled to 10° C, containing 80 mmol of 3-formyl-4-hydroxybenzoic acid (prepared according to H. WYMBERG, J. Am. Chem. Soc., 76, 4998, 1954) and 87 mmol of N-hydroxysuccinimide in 320 ml of chloroform. After re-equilibrating to room temperature, the mixture is kept stirring overnight. The precipitate is then filtered. The filtrate is cooled to 8° C. and treated dropwise, with stirring, with a suspension containing 160 mmol of phenylalanine methyl ester hydrochloride and 160 mmol of triethylamine in 100 ml of anhydrous dimethylformamide. The mixture is stirred for 3 hours at 20° C. and then for 5 hours at 50° C. After cooling and evaporation of the solvents, the residue is taken up in 400 ml of ethyl acetate. After washing this solution with 1N hydrochloric acid and then with water, the organic phase is dried and evaporated. The oily residue leads to the expected product by crystallization from toluene.

Workup

  1. customAfter re-equilibrating to room temperature
  2. filtrationThe precipitate is then filtered
  3. temperatureThe filtrate is cooled to 8° C.
  4. additiontreated dropwise
  5. stirringwith stirring, with a suspension
  6. stirringThe mixture is stirred for 3 hours at 20° C.
  7. waitfor 5 hours at 50° C
  8. temperatureAfter cooling
  9. customevaporation of the solvents
  10. washAfter washing this solution with 1N hydrochloric acid
  11. dry with materialwith water, the organic phase is dried
  12. customevaporated
  13. customThe oily residue leads to the expected product by crystallization from toluene

Sources & evidence

ORD record
ord-19edb5935d794d2d9e009e8c3b92da74
Source dataset
uspto-grants-1993_11
Patent number
US05266565

Reaction notes

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