(S)-3-fluoropyrrolidine → 5-Bromo-2-((S)-3-fluoro-pyrrolidin-1-yl)-nicotinonitrile

HRID 55860Notes

Reaction equation

HRID 55860 reaction equation
[Br:1][C:2]1[CH:3]=[N:4][C:5](F)=[C:6]([CH:9]=1)[C:7]#[N:8].[F:11][C@H:12]1[CH2:16][CH2:15][NH:14][CH2:13]1>CC#N>[Br:1][C:2]1[CH:3]=[N:4][C:5]([N:14]2[CH2:15][CH2:16][C@H:12]([F:11])[CH2:13]2)=[C:6]([CH:9]=1)[C:7]#[N:8]

Participants

4

Reactant 2

HCID 7016277(S)-3-fluoropyrrolidineHCID 848197325-Bromo-2-fluoropyridine-3-carbonitrile

Product 1

HCID 903566975-Bromo-2-((S)-3-fluoro-pyrrolidin-1-yl)-nicotinonitrile

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

5-Bromo-2-fluoro-nicotinonitrile (4) (5.0 g, 24.9 mmol) and (S)-(+)-3-fluoropyrrolidine (3.3 g, 25.9 mmol) were dissolved in dry MeCN (100 mL). TEA (8.0 mL, 57.4 mol) was added and the mixture stirred at rt for 2 hours. The solvent was evaporated in vacuo and the residue partitioned between H2O (100 mL) and EtOAc (100 mL). The organic phase was washed with saturated brine solution (100 mL), then dried (MgSO4), filtered and the solvent evaporated in vacuo. The residue was dissolved in DCM (100 mL) and the solvent evaporated in vacuo. The title compound was obtained as an off-white solid (6.3 g, 94%); LCMS, Rt=2.86 min (MeOH-FA method), m/z 270, 272 (MH+).

Workup

  1. customThe solvent was evaporated in vacuo
  2. customthe residue partitioned between H2O (100 mL) and EtOAc (100 mL)
  3. washThe organic phase was washed with saturated brine solution (100 mL)
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customthe solvent evaporated in vacuo
  7. dissolutionThe residue was dissolved in DCM (100 mL)
  8. customthe solvent evaporated in vacuo

Sources & evidence

ORD record
ord-90b3c37bfa2348d2a8da72af9a9b47bb
Source dataset
uspto-grants-2016_09
Patent number
US09433622B2

Reaction notes

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