Water → (S)-benzyl 4-(3-(2,5-difluoro-4-(methylsulfonyl)phenylamino)-2-oxopyrrolidin-1-yl)piperidine-1-carboxylate

HRID 407889

Reaktionsgleichung

Reaktionsgleichung von HRID 407889
[NH2:1][C@H:2]1[CH2:6][CH2:5][N:4]([CH:7]2[CH2:12][CH2:11][N:10]([C:13]([O:15][CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)=[O:14])[CH2:9][CH2:8]2)[C:3]1=[O:23].[F:24][C:25]1[CH:30]=[C:29]([S:31]([CH3:34])(=[O:33])=[O:32])[C:28]([F:35])=[CH:27][C:26]=1F.C([O-])([O-])=O.[Na+].[Na+].O>CS(C)=O>[F:24][C:25]1[CH:30]=[C:29]([S:31]([CH3:34])(=[O:33])=[O:32])[C:28]([F:35])=[CH:27][C:26]=1[NH:1][C@H:2]1[CH2:6][CH2:5][N:4]([CH:7]2[CH2:12][CH2:11][N:10]([C:13]([O:15][CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)=[O:14])[CH2:9][CH2:8]2)[C:3]1=[O:23]

Komponenten

6

Edukt 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 467393961,2,4-Trifluoro-5-(methylsulfonyl)benzeneHCID 86688074(S)-benzyl 4-(3-amino-2-oxopyrrolidin-1-yl)piperidine-1-carboxylate

Produkt 1

HCID 86688081(S)-benzyl 4-(3-(2,5-difluoro-4-(methylsulfonyl)phenylamino)-2-oxopyrrolidin-1-yl)piperidine-1-carboxylateAusbeute 65 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 679Dimethyl SulfoxideLösungsmittel

Reaktionsbedingungen

Temperatur
130 °C

Versuchsvorschrift

A solution of (S)-benzyl 4-(3-amino-2-oxopyrrolidin-1-yl)piperidine-1-carboxylate (2.5, 7.9 mmol) (Preparation E, Step D), 1,2,4-trifluoro-5-(methylsulfonyl)benzene (3.3 g, 16 mmol), and Na2CO3 (2.5 g, 24 mmol) in DMSO (20 mL) was degassed using nitrogen and was stirred at 130° C. for 18 hours in a sealed tube. The reaction mixture was poured into water (200 mL) and extracted with EtOAc (3×100 mL). The combined organic layers were washed with brine and dried over MgSO4, filtered then concentrated in vacuo. The material was purified over silica gel (100% EtOAc) to yield (S)-benzyl 4-(3-(2,5-difluoro-4-(methylsulfonyl)phenylamino)-2-oxopyrrolidin-1-yl)piperidine-1-carboxylate (2.6 g, 5.1 mmol, 65%).

Aufarbeitung

  1. extractionextracted with EtOAc (3×100 mL)
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationthen concentrated in vacuo
  6. customThe material was purified over silica gel (100% EtOAc)

Quellen und Nachweise

ORD-Eintrag
ord-2f9a8c94b05e45cea0c30c2e681ae181
Quelldatensatz
uspto-grants-2014_06
Patentnummer
US08754226B2

Verknüpfte Notizen

Wird geladen…