Sulfuric Acid → 2-(3-(3,4-Dichlorophenyl)pyrrolidin-3-yl)ethanol

HRID 343504Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 343504
[H-].[Al+3].[Li+].[H-].[H-].[H-].S(=O)(=O)(O)O.S(=O)(=O)(O)O.O1CCCC1.C([O:24][C:25](=O)[CH2:26][C:27]1([C:33]2[CH:38]=[CH:37][C:36]([Cl:39])=[C:35]([Cl:40])[CH:34]=2)[CH2:31][C:30](=O)[NH:29][CH2:28]1)C>O1CCCC1.ClCCl.C(OCC)(=O)C.CCCCCC>[Cl:40][C:35]1[CH:34]=[C:33]([C:27]2([CH2:26][CH2:25][OH:24])[CH2:31][CH2:30][NH:29][CH2:28]2)[CH:38]=[CH:37][C:36]=1[Cl:39]

Komponenten

8

Edukt 4

HCID 1118Sulfuric Acid2×HCID 21226445Aluminium lithium hydride2×HCID 54080079(3-(3,4-Dichlorophenyl)-5-oxopyrrolidin-3-yl)acetic acid ethyl esterHCID 68124251Sulfuric acid tetrahydrofuran

Produkt 1

HCID 184644272-(3-(3,4-Dichlorophenyl)pyrrolidin-3-yl)ethanol

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 6344DichloromethaneLösungsmittelHCID 8028TetrahydrofuranLösungsmittel3×HCID 21226206Ethyl acetate hexaneLösungsmittel

Versuchsvorschrift

Cool a solution of lithium aluminum hydride (450 mL, 1M in tetrahydrofuran, 450 mmol) to -10° C. in a ice/acetone bath. Add dropwise, a solution of sulfuric acid (12 mL, 99.999%, 225.3 mmol) in tetrahydrofuran (35 mL). (Use caution when adding the sulfuric acid to the tetrahydrofuran and also when adding the sulfuric acid/tetrahydrofuran solution to the lithium aluminum hydride solution). After the addition is complete, stir for 1 hour. Warm to ambient temperature and stir for 2 hours. Add dropwise, a solution of (3-(3,4-dichlorophenyl)-5-oxopyrrolidin-3-yl)acetic acid ethyl ester (23.2 g, 73.4 mmol) in tetrahydrofuran (70 mL). Heat to 45°-50° C. for 36 hours. Cool in an ice bath. Add dropwise, a solution of tetrahydrofuran/water (1/1, 70 mL). Filter and rinse the filter cake with Tetrahydrofuran and dichloromethane, retain the filtrate. Combine the filter cake with tetrahydrofuran/water/15% sodium hydroxide solution (1 L/70 mL/20 mL) and vigorously stir for 2 hours. Filter and combine the filtrate with the filtrate obtained above. Concentrate the combined filtrates invacuo to obtain a residue. Dissolve the residue in dichloromethane and dry over MgSO4, filter, and concentrate invacuo to obtain a residue. Recrystallize the residue from diethyl ether to give the title compound: Rf= 0.27 (silica gel, 9/1/0.2 dichloromethane/methanol/ammonium hydroxide); mp; 91°-94° C.

Aufarbeitung

  1. additionAdd dropwise
  2. additionAfter the addition
  3. stirringstir for 2 hours
  4. additionAdd dropwise
  5. temperatureHeat to 45°-50° C. for 36 hours
  6. temperatureCool in an ice bath
  7. additionAdd dropwise
  8. filtrationFilter
  9. washrinse the filter cake with Tetrahydrofuran and dichloromethane
  10. stirringvigorously stir for 2 hours
  11. filtrationFilter
  12. customobtained above
  13. concentrationConcentrate the combined filtrates
  14. customto obtain a residue
  15. dry with materialdry over MgSO4
  16. filtrationfilter
  17. concentrationconcentrate invacuo
  18. customto obtain a residue
  19. customRecrystallize the residue from diethyl ether

Quellen und Nachweise

ORD-Eintrag
ord-fbbaac1848db47f4ac16de0f99133332
Quelldatensatz
uspto-grants-1999_01
Patentnummer
US05861417

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