Cesium carbonate → HCID 86700361, compound

HRID 879539Notes

Reaction equation

HRID 879539 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-])=O)=[C:4](F)[CH:3]=1.C([O-])([O-])=O.[Cs+].[Cs+].[NH2:18][C@H:19]1[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20]1.[CH3:31][C:32](OCC)(OCC)OCC>CN(C=O)C.CCOC(C)=O.O.CCO.CCOC(C)=O.CC(O)=O.[Pt]>[Br:1][C:2]1[CH:7]=[CH:6][C:5]2[N:8]=[C:31]([CH3:32])[N:18]([C@H:19]3[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20]3)[C:4]=2[CH:3]=1

Participants

11

Reactant 4

HCID 10796Cesium carbonateHCID 66221Triethyl orthoacetateHCID 854071tert-butyl (3S)-3-aminopyrrolidine-1-carboxylateHCID 27833624-Bromo-2-fluoro-1-nitrobenzene

Product 1

HCID 86700361HCID 86700361, compound

Reagents, catalysts & solvents 6

HCID 23939PlatinumCatalystHCID 176Acetic AcidSolventHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 21584252Ethanol ethylacetateSolvent

Procedure

A flask was charged with 4-bromo-2-fluoro-1-nitrobenzene (531 mg, 2.41 mmol), Cs2CO3 (2.43 g, 7.46 mmol) and diluted with DMF (6 mL). The reaction mixture was then treated with (S)-tert-butyl 3-aminopyrrolidine-1-carboxylate (0.9 mL, 5.16 mmol) at room temperature and allowed to stir for 16 hours. The mixture was diluted with EtOAc and H2O and the layers were separated. The aqueous layer was extracted with EtOAc and the combined organic extracts were dried over Na2SO4, filtered through a small pad of silica gel eluting with 30% EtOAc/Hex, and concentrated in vacuo to afford a crude residue. The flask containing the crude residue was charged with 5 wt % Pt/C (211 mg) and then diluted with 2:1 EtOH/EtOAc (16 mL). The flask was evacuated then backfilled with H2 (3 cycles) and stirred under a hydrogen atmosphere for 20 minutes, at which time, the flask was purged with N2, filtered through a pad of Celite, and concentrated in vacuo to provide a crude residue that was then taken up in AcOH (5 mL). To this was added MeC(OEt)3 (0.5 mL) at room temperature and stirred for 15 minutes, at which time, the solution was concentrated in vacuo. The crude residue was purified by silica gel column chromatography (0-50% THF/CH2Cl2 gradient) to afford the desired product. LCMS-ESI+: calc'd C17H23BrN3O2: 380.1 (M+H1); Found: 380.1 (M+H+).

Workup

  1. customthe layers were separated
  2. extractionThe aqueous layer was extracted with EtOAc
  3. dry with materialthe combined organic extracts were dried over Na2SO4
  4. filtrationfiltered through a small pad of silica gel eluting with 30% EtOAc/Hex
  5. concentrationconcentrated in vacuo
  6. customto afford a crude residue
  7. customThe flask was evacuated
  8. stirringstirred under a hydrogen atmosphere for 20 minutes, at which time
  9. customthe flask was purged with N2
  10. filtrationfiltered through a pad of Celite
  11. concentrationconcentrated in vacuo
  12. customto provide a crude residue that
  13. stirringstirred for 15 minutes, at which time
  14. concentrationthe solution was concentrated in vacuo
  15. customThe crude residue was purified by silica gel column chromatography (0-50% THF/CH2Cl2 gradient)

Sources & evidence

ORD record
ord-b84f0f382b6d427ab9f9f3ee32d5dcae
Source dataset
uspto-grants-2015_03
Patent number
US08987250B2

Reaction notes

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