Formaldehyde → (+/-)-(4R*,5R*)-5-[(1S*)-hydroxy(5-phenyl(2-thienyl))methyl]methyl-4-[4-(methylamino)phenyl]pyrrolidin-2-one

HRID 1838004Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1838004
[OH:1][C@H:2]([C:17]1[S:18][C:19]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[CH:20][CH:21]=1)[C@@H:3]1[N:7]([CH3:8])[C:6](=[O:9])[CH2:5][C@@H:4]1[C:10]1[CH:15]=[CH:14][C:13]([NH2:16])=[CH:12][CH:11]=1.[CH2:28]=O.C[O-].[Na+].[BH4-].[Na+].[OH-].[Na+]>CO.O>[OH:1][C@H:2]([C:17]1[S:18][C:19]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[CH:20][CH:21]=1)[C@@H:3]1[N:7]([CH3:8])[C:6](=[O:9])[CH2:5][C@@H:4]1[C:10]1[CH:11]=[CH:12][C:13]([NH:16][CH3:28])=[CH:14][CH:15]=1

Komponenten

8

Edukt 5

HCID 712FormaldehydeHCID 14798Sodium HydroxideHCID 4311764Sodium borohydrideHCID 10271018(+/-)-(4R*,5R*)-5-[(1S*)-hydroxy(5-phenyl(2-thienyl))methyl]-4-(4-aminophenyl)-1-methylpyrrolidin-2-oneHCID 10942334Sodium Methoxide

Produkt 1

HCID 59066505(+/-)-(4R*,5R*)-5-[(1S*)-hydroxy(5-phenyl(2-thienyl))methyl]methyl-4-[4-(methylamino)phenyl]pyrrolidin-2-oneAusbeute 76 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 887MethanolLösungsmittelHCID 962WaterLösungsmittel

Versuchsvorschrift

A mixture of (±)-(4R*,5R*)-5-[(1S*)-hydroxy(5-phenyl(2-thienyl))methyl]-4-(4-aminophenyl)-1-methylpyrrolidin-2-one (Example 17, 105 mg, 0.30 mmol), paraformaldehyde (13 mg, 0.42 mmol) and sodium methoxide (81 mg, 1.5 mmol) in methanol (1 mL) was stirred overnight. After adding sodium borohydride (12 mg, 0.30 mmol) the reaction mixture was heated at the reflux temperature for 1 h, then treated with a 1M NaOH solution (1 mL). The resulting mixture was stirred for 10 min, diluted with water (10 mL) and extracted with EtOAc (2×10 mL). The organic layer was washed with a saturated NaCl solution, dried (Na2SO4) and concentrated under reduced pressure to give a yellow solid. The crude product was sequentially triturated with EtOAc, Et2O and hexane to provide (±)-(4R*,5R*)-5-[(1S*)-hydroxy(5-phenyl(2-thienyl))methyl]methyl-4-[4-(methylamino)phenyl]pyrrolidin-2-one (89 mg, 76%) as a white solid: TLC (EtOAc) Rf 0.34; mp: 212° C.

Aufarbeitung

  1. temperaturewas heated at the reflux temperature for 1 h
  2. stirringThe resulting mixture was stirred for 10 min
  3. extractionextracted with EtOAc (2×10 mL)
  4. washThe organic layer was washed with a saturated NaCl solution
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated under reduced pressure
  7. customto give a yellow solid
  8. customThe crude product was sequentially triturated with EtOAc, Et2O and hexane

Quellen und Nachweise

ORD-Eintrag
ord-c6815c49241c4635b7951d4532b033ca
Quelldatensatz
uspto-grants-2004_08
Patentnummer
US06784167B2

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