Cesium carbonate → HCID 66673757, compound

HRID 423402Notes

Reaction equation

HRID 423402 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.CCOC(C)=O>[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 60052341HCID 60052341, compound

Product 1

HCID 66673757HCID 66673757, compoundYield 100%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

Dissolve methanesulfonic acid (R)-1-(5-bromo-pyridin-2-yl)-pyrrolidin-3-yl ester (0.23 g, 0.71 mmol) and (R)-3-fluoro-pyrrolidine hydrochloride (107 mg, 0.85 mmol) in DMF (5 mL) and add Cs2CO3 (0.69 g, 2.13 mmol). Warm to 70° C. overnight. Dilute with EtOAc (100 mL) and wash with H2O (3×100 mL). Dry with Na2SO4, filter, and concentrate. Purify the crude material by chromatography, eluting with 75-100% EtOAc/hexane to give 0.22g (100%) of the title compound. 1H-NMR (CDCl3), δ 1.87-2.00 (m, 1H), 2.00-2.09 (m, 1H), 2.18-2.30 (m, 2H), 3.40-3.80 (m, 9H), 5.10-5.28 (m, 1H), 5.34-5.40 (m, 1H), 6.28 (d, J=9.0 Hz, 1H), 7.51 (dd, J=9.0, 2.4 Hz, 1H), 8.18 (d, J=2.4 Hz, 1H).

Workup

  1. washwash with H2O (3×100 mL)
  2. dry with materialDry with Na2SO4
  3. filtrationfilter
  4. concentrationconcentrate
  5. customPurify the crude material by chromatography
  6. washeluting with 75-100% EtOAc/hexane

Sources & evidence

ORD record
ord-b48a8179921740bdaedb8f8ee23c0804
Source dataset
uspto-grants-2012_01
Patent number
US08101764B2

Reaction notes

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