Cesium carbonate → (3R,3'R)-1'-(5-Bromo-pyridin-2-yl)-3-fluoro-[1,3']bipyrrolidinyl

HRID 423425Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 423425
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[CH2:12][CH2:11][C@H:10](OS(C)(=O)=O)[CH2:9]2)=[N:6][CH:7]=1.Cl.[F:19][C@@H:20]1[CH2:24][CH2:23][NH:22][CH2:21]1.C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C.ClCCl>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[CH2:12][CH2:11][C@@H:10]([N:22]3[CH2:23][CH2:24][C@@H:20]([F:19])[CH2:21]3)[CH2:9]2)=[N:6][CH:7]=1

Komponenten

6

Edukt 3

HCID 10796Cesium carbonateHCID 2759162(3R)-3-fluoropyrrolidine hydrochlorideHCID 86638154methanesulfonic acid (S)-1-(5-bromo-pyridin-2-yl)-pyrrolidin-3-yl ester

Produkt 1

HCID 66673622(3R,3'R)-1'-(5-Bromo-pyridin-2-yl)-3-fluoro-[1,3']bipyrrolidinylAusbeute 39 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
70 °C

Versuchsvorschrift

Dissolve methanesulfonic acid (S)-1-(5-bromo-pyridin-2-yl)-pyrrolidin-3-yl ester (3 g, 9.34 mmol) and (R)-3-fluoro-pyrrolidine hydrochloride (1.00 g, 11.21 mmol) in DMF (50 mL) and add Cs2CO3 (9.13 g, 28.02 mmol). Warm to 70° C. overnight. Dilute with dichloromethane (3×40 mL), wash with H2O (50 mL) and brine. Dry with Na2SO4, filter, and concentrate the organic solution. Purify the crude material by chromatography, eluting with 0-50% EtOAc/hexane, to give 1.14 g (39%) of (3R,3′R)-1′-(5-Bromo-pyridin-2-yl)-3-fluoro-[1,3′]bipyrrolidinyl.

Aufarbeitung

  1. washwash with H2O (50 mL) and brine
  2. dry with materialDry with Na2SO4
  3. filtrationfilter
  4. concentrationconcentrate the organic solution
  5. customPurify the crude material by chromatography
  6. washeluting with 0-50% EtOAc/hexane

Quellen und Nachweise

ORD-Eintrag
ord-caaafbcdee4c4c3ab3d718c11f535d20
Quelldatensatz
uspto-grants-2012_01
Patentnummer
US08101764B2

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