L-Pyroglutamic Acid → L-Pyroglutamyl-L-phenylalanine Methyl Ester

HRID 4497

Reaktionsgleichung

Reaktionsgleichung von HRID 4497
CN1CCOCC1.ClC(OCC(C)C)=O.[NH:16]1[C:20](=[O:21])[CH2:19][CH2:18][C@H:17]1[C:22]([OH:24])=O.Cl.[CH3:26][O:27][C:28](=[O:38])[C@H:29]([CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)[NH2:30]>C1COCC1.CN(C=O)C.CN(C=O)C.CCOC(C)=O.CC(O)=O>[CH3:26][O:27][C:28](=[O:38])[C@H:29]([CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)[NH:30][C:22](=[O:24])[C@@H:17]1[CH2:18][CH2:19][C:20](=[O:21])[NH:16]1

Komponenten

8

Edukt 4

HCID 7405L-Pyroglutamic AcidHCID 79724-Methylmorpholine2×HCID 62365Isobutyl chloroformateHCID 75736Methyl L-phenylalaninate hydrochloride

Produkt 1

HCID 12378871L-Pyroglutamyl-L-phenylalanine Methyl Ester

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 6228DimethylformamideLösungsmittelHCID 21974620tetrahydrofuran N,N-dimethylformamideLösungsmittelHCID 22609514Ethyl acetate acetateLösungsmittel

Versuchsvorschrift

N-Methylmorpholine (2.02 g, 0.020 mol) and isobutyl chloroformate (2.73 g, 0.020 mol) were added to a solution of L-pyroglutamic acid (2.58 g, 0.020 mol) in 100 ml of THF/DMF (6:1) at -15° C. After a 2 minute coupling period, a mixture of L-phenylalanine methyl ester hydrochloride (4.31 g, 0.020 mol) (suspension) and N-methyl morpholine (2.02 g, 0.020 mol) in 50 ml of DMF was added to the reaction mixture. The reaction was allowed to proceed at this temperature for 30 minutes and then at room temperature for 1 additional hour. The reaction mixture was then filtered to remove fines and the filtrate was evaporated in vacuo to incipient dryness. The resulting yellow liquid was dissolved in 100 ml of ethyl acetate, and the ethyl acetate solution was washed with 5% citric acid saturated with sodium chloride (50 ml) and 5% sodium bicarbonate saturated with NaCl (50 ml). The separated organic layer was dried over anhydrous sodium sulfate and evaporated in vacuo to yield quantitative amounts of a pale yellow liquid which was used directly for the following step. TLC: Rf =0.22 in EtOAc/AcOH (100:1), detected by UV quenching; IR (neat, cm-1) 3300 (NH), 3020-3060 (C6H5), 2860-2960 (alkyl), 1650-1750 (C=O); NMR (Silanor C, δ from TMS) 7.25 (fused s, C6H5 --), 5.5-5.7 and 6.6-6.8 (broad, NH's), 4.6-5.1 (g, --NH--CH--C=O), 3.0-3.2 (q, --CH2 --C6H5), 1.6-2.5 (m, cycl. O=C--CH2 --CH2).

Aufarbeitung

  1. additionwas added to the reaction mixture
  2. waitto proceed at this temperature for 30 minutes
  3. customat room temperature
  4. filtrationThe reaction mixture was then filtered
  5. customto remove fines
  6. customthe filtrate was evaporated in vacuo
  7. dissolutionThe resulting yellow liquid was dissolved in 100 ml of ethyl acetate
  8. washthe ethyl acetate solution was washed with 5% citric acid saturated with sodium chloride (50 ml) and 5% sodium bicarbonate saturated with NaCl (50 ml)
  9. dry with materialThe separated organic layer was dried over anhydrous sodium sulfate
  10. customevaporated in vacuo
  11. customto yield quantitative amounts of a pale yellow liquid which
  12. customquenching

Quellen und Nachweise

ORD-Eintrag
ord-c4b5968c16f543fc8c35e4b753328296
Quelldatensatz
uspto-grants-1988_02
Patentnummer
US04726941

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