Ethanol → (5-Fluoropyridin-3-yl)methanamine

HRID 911310Notes

Reaction equation

HRID 911310 reaction equation
Cl[C:2]1[C:7]([C:8]#[N:9])=[CH:6][C:5]([F:10])=[C:4](Cl)[N:3]=1.C(O)C.[H][H]>[Pd].C(N(CC)CC)C>[NH2:9][CH2:8][C:7]1[CH:2]=[N:3][CH:4]=[C:5]([F:10])[CH:6]=1

Participants

6

Reactant 3

HCID 702EthanolHCID 27338492,6-Dichloro-5-fluoro-3-pyridinecarbonitrileHCID 178418361HCID 178418361, compound

Product 1

HCID 45116207(5-Fluoropyridin-3-yl)methanamine

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8471TriethylamineSolvent

Procedure

In a Parr Bottle add 2,6-dichloro-3-cyano-5-fluoropyridine (20 g, 0.105 mol), ethanol (336 mL), triethylamine (24 mL), and 5% Pd/C (4 g). Place on a Parr Shaker Apparatus under 60 psi hydrogen for 1 h at ambient temperature. Filter the reaction mixture and bubble ammonia gas into filtrate for 10 min. Add Raney® nickel (5.2 g) and place on a Parr Shaker Apparatus under 500 psi hydrogen for 18 h at 60-70° C. Filter the reaction mixture and concentrate in vacuo. Dissolve in methanol and add 1N hydrogen chloride in ether until form a precipitate. Cool in an ice bath, filter off the precipitate, wash the solid several times with ether, and dry to give the title compound as the hydrochloride salt (12 g, 70%). MS (ES+) m/z: 127 (M+H)+. Dissolve the hydrochloride salt in water, add 0.1 N aqueous NaOH to adjust to pH 10, extract with DCM, dry the organic layer over Na2SO4, filter and concentrate to give the title compound.

Workup

  1. filtrationFilter the reaction mixture
  2. custombubble ammonia gas into filtrate for 10 min
  3. filtrationFilter the reaction mixture
  4. concentrationconcentrate in vacuo
  5. dissolutionDissolve in methanol
  6. additionadd 1N hydrogen chloride in ether until form a precipitate
  7. temperatureCool in an ice bath
  8. filtrationfilter off the precipitate
  9. washwash the solid several times with ether
  10. customdry

Sources & evidence

ORD record
ord-8f13e3fcb4214d249d720dd235516182
Source dataset
uspto-grants-2011_09
Patent number
US08022062B2

Reaction notes

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