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

HRID 423425Notes

Reaction equation

HRID 423425 reaction equation
[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

Participants

6

Reactant 3

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

Product 1

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

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
70 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-caaafbcdee4c4c3ab3d718c11f535d20
Source dataset
uspto-grants-2012_01
Patent number
US08101764B2

Reaction notes

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