Triethylamine → 2-((2-(1,3-Dithiol-2-ylidene)-3-methoxy-3-oxopropanoyl)amino)-5-methoxy-5-oxopentanoic acid

HRID 1737938Notes

Reaction equation

HRID 1737938 reaction equation
[S:1]1[CH:5]=[CH:4][S:3][C:2]1=[C:6]([C:10]([O:12][CH3:13])=[O:11])[C:7]([OH:9])=O.C(N(CC)CC)C.[C:21](Cl)(=[O:25])[O:22][CH2:23]C.CC(O[CH2:31][CH2:32][C@H:33]([NH2:37])[C:34]([OH:36])=[O:35])=O>ClCCl>[S:3]1[CH:4]=[CH:5][S:1][C:2]1=[C:6]([C:10]([O:12][CH3:13])=[O:11])[C:7]([NH:37][CH:33]([CH2:32][CH2:31][C:21]([O:22][CH3:23])=[O:25])[C:34]([OH:36])=[O:35])=[O:9]

Participants

6

Reactant 4

HCID 8471Triethylamine2×HCID 10928Ethyl chloroformateHCID 439389O-AcetylhomoserineHCID 15432125(1,3-Dithiol-2-ylidene)malonic acid monomethyl ester

Product 1

HCID 154321262-((2-(1,3-Dithiol-2-ylidene)-3-methoxy-3-oxopropanoyl)amino)-5-methoxy-5-oxopentanoic acidYield 91%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

2-(1,3-Dithiol-2-ylidene)-3-methoxy-3-oxopropionic acid (3) (109 g) was suspended in dichloromethane (1 l), followed by the addition of 61 g of triethylamine under ice-cooled stirring. To the resulting mixture, ethyl chlorocarbonate (60 g) was added dropwise under ice-cooled stirring over 30 minutes. To a solution of 88.5 g of γ-methyl L-glutamate and 61 g of triethylamine in dichloromethane (1 l), the thus-obtained solution was added dropwise at 10° C. over 1.5 hours. After the resulting mixture was stirred at room temperature for 10 hours, the solvent was removed under reduced pressure. Ethyl acetate (2 l) was added to the residue, and the resultant precipitate was filtered off. After the filtrate was washed with 1 N hydrochloric acid and then with water, the solvent was removed under reduced pressure. The residue was dissolved in methanol (800 ml). Activated carbon (15 g) was added, followed by stirring at 40° C. for 1 hour. The activated carbon was filtered off, and the methanol was removed under reduced pressure. The residue was dissolved in toluene (500 ml) and the toluene was then removed under reduced pressure, whereby 2-((2-(1,3-dithiol-2-ylidene)-3-methoxy-3-oxopropanoyl)amino)-5-methoxy-5-oxopentanoic acid (4) (164 g, yield: 91%) was obtained as a brown oil.

Workup

  1. temperaturecooled
  2. temperaturecooled
  3. stirringstirring over 30 minutes
  4. stirringAfter the resulting mixture was stirred at room temperature for 10 hours
  5. customthe solvent was removed under reduced pressure
  6. additionEthyl acetate (2 l) was added to the residue
  7. filtrationthe resultant precipitate was filtered off
  8. washAfter the filtrate was washed with 1 N hydrochloric acid
  9. customwith water, the solvent was removed under reduced pressure
  10. dissolutionThe residue was dissolved in methanol (800 ml)
  11. additionActivated carbon (15 g) was added
  12. stirringby stirring at 40° C. for 1 hour
  13. filtrationThe activated carbon was filtered off
  14. customthe methanol was removed under reduced pressure
  15. dissolutionThe residue was dissolved in toluene (500 ml)
  16. customthe toluene was then removed under reduced pressure

Sources & evidence

ORD record
ord-2586c6f1fd4145ae8a59dc65b85dfe2e
Source dataset
uspto-grants-1999_10
Patent number
US05962509

Reaction notes

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