2-Thiopheneacetic acid → 1-[3-(4-tert-butylbenzoyl)propionyl]-L-proline

HRID 903473Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 903473
[C:1]([C:5]1[CH:17]=[CH:16][C:8]([C:9]([CH2:11][CH2:12][C:13]([OH:15])=O)=[O:10])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[NH:18]1[CH2:25][CH2:24][CH2:23][C@H:19]1[C:20]([OH:22])=[O:21].C(=O)(O)[O-].[Na+].BrBr.C[O-].[Na+].S1C=CC=C1CC(O)=O>O.C(O)(=O)C.C(O)C.C(O)C.O>[C:1]([C:5]1[CH:6]=[CH:7][C:8]([C:9]([CH2:11][CH2:12][C:13]([N:18]2[CH2:25][CH2:24][CH2:23][C@H:19]2[C:20]([OH:22])=[O:21])=[O:15])=[O:10])=[CH:16][CH:17]=1)([CH3:2])([CH3:3])[CH3:4]

Komponenten

11

Edukt 6

HCID 159702-Thiopheneacetic acidHCID 24408BromineHCID 145742L-ProlineHCID 516892Sodium BicarbonateHCID 20640374-(4-Tert-butylphenyl)-4-oxobutanoic acidHCID 10942334Sodium Methoxide

Produkt 1

HCID 540369431-[3-(4-tert-butylbenzoyl)propionyl]-L-proline

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 176Acetic AcidLösungsmittel2×HCID 702EthanolLösungsmittelHCID 962WaterLösungsmittelHCID 19096565Water ethanolLösungsmittel

Versuchsvorschrift

As for example 85, 14 g. of 3-(4-tert-butylbenzoyl)-propionic acid is reacted with 6.9 g. of N-hydroxysuccinimide in the presence of 12.36 g. of N,N-dicyclohexylcarbodiimide to give 15.5 g. of 3-(4-tert-butylbenzoyl)propionic acid, N-hydroxysuccinimide ester, m.p. 135°-138° C. The preceding compound is added to a solution of 8.05 g. of L-proline and 11.76 g. of sodium bicarbonate in 400 ml. of ethanol-water (1:1). The mixture is stirred overnight, filtered and the filtrate concentrated under vacuum. The mixture is acidified with concentrated hydrochloric acid and extracted with dichloromethane. The solvent is removed to give an amber gum which chromatographed on 150 g. of silica gel with hexane-ethyl acetate (1:1) containing 2% acetic acid as solvent. From the column is obtained 12.4 g. of glass. To a solution of 9.8 g. of the preceding glass in 150 ml. of acetic acid is added 4.8 g. of bromine. The mixture is stirred overnight, concentrated and poured into ice and water. The mixture is extracted with dichloromethane and the extract concentrated to give 12.1 g. of a glass. The preceding glass is added to a solution of 1.94 g. of sodium methoxide and 4.56 g. of thiolacetic acid in 50 ml. of ethanol. After stirring for 2 hours, 1 ml. of acetic acid is added and the mixture diluted with water. The mixture is extracted with dichloromethane, the extract washed with water, dried (MgSO4) and the solvent removed to give 12 g. of product as a yellow glass.

Aufarbeitung

  1. additionThe preceding compound is added to a solution of 8.05 g
  2. filtrationfiltered
  3. concentrationthe filtrate concentrated under vacuum
  4. extractionextracted with dichloromethane
  5. customThe solvent is removed
  6. customto give an amber gum which
  7. customchromatographed on 150 g
  8. additionof silica gel with hexane-ethyl acetate (1:1) containing 2% acetic acid as solvent
  9. customFrom the column is obtained 12.4 g
  10. stirringThe mixture is stirred overnight
  11. concentrationconcentrated
  12. additionpoured into ice and water
  13. extractionThe mixture is extracted with dichloromethane
  14. concentrationthe extract concentrated
  15. customto give 12.1 g
  16. additionThe preceding glass is added to a solution of 1.94 g
  17. stirringAfter stirring for 2 hours
  18. extractionThe mixture is extracted with dichloromethane
  19. washthe extract washed with water
  20. dry with materialdried (MgSO4)
  21. customthe solvent removed
  22. customto give 12 g

Quellen und Nachweise

ORD-Eintrag
ord-9e1cd55590c84b0eb12155fa23e1ac6e
Quelldatensatz
uspto-grants-1980_10
Patentnummer
US04226775

Notizen zur Reaktion

Wird geladen…