4-Fluoro-3-methoxybenzonitrile → 4-Fluoro-3-methoxybenzylamine

HRID 1178950Notes

Reaction equation

HRID 1178950 reaction equation
[F:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][C:3]=1[O:10][CH3:11].[H][H]>[Pd].C(O)(=O)C>[F:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][NH2:7])=[CH:4][C:3]=1[O:10][CH3:11]

Participants

5

Reactant 2

HCID 27373654-Fluoro-3-methoxybenzonitrileHCID 178418361HCID 178418361, compound

Product 1

HCID 442031244-Fluoro-3-methoxybenzylamineYield 134%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 176Acetic AcidSolvent

Procedure

Add 4-fluoro-3-methoxy-benzonitrile (2 g, 0.01 mol), 10% palladium on carbon (0.400 g) and glacial acetic acid (120 ml) to a pressure vessel. Purge the reaction vessel with nitrogen, purge the reaction vessel with hydrogen, pressurize the reaction mixture with hydrogen (415 Kpa), seal the vessel, and agitate the reaction. After 8 hours stop the agitation, vent the excess hydrogen from the vessel and purge the vessel with nitrogen. Filter the reaction mixture to remove the 5% palladium on carbon and return the filtrate for product isolation. Concentrate the crude solution, re-dissolve in CH2Cl2 (80 mL) and wash with 5N NaOH (35 mL). Separate the organic and aqueous phases and extract the aqueous with additional CH2Cl2 (20 mL). Combine the organic solutions, dry, filter and concentrate to give the crude material 2.08 g (100%). The title compound as the major product (Rf=0.12, 10% MeOH/CH2Cl2) is used without further purification. MS (ES+) 156.1 (M+1)+. 1H NMR (400 MHz, CDCl3): δ 7.01(dd, 1H, J=8.2, 11.4), 6.95 (dd, 1H, J=2.1, 8.4), 6.80 (m, 1H), 3.89 (s, 3H), 3.82 (s, 2H), 1.54 (br s, 2H).

Workup

  1. customPurge the reaction vessel with nitrogen
  2. custompurge the reaction vessel with hydrogen
  3. customseal the vessel
  4. customthe reaction
  5. custompurge the vessel with nitrogen
  6. filtrationFilter the reaction mixture
  7. customto remove the 5% palladium on carbon
  8. concentrationConcentrate the crude solution
  9. dissolutionre-dissolve in CH2Cl2 (80 mL)
  10. washwash with 5N NaOH (35 mL)
  11. customSeparate the organic and aqueous phases
  12. extractionextract the aqueous with additional CH2Cl2 (20 mL)
  13. customCombine the organic solutions, dry
  14. filtrationfilter
  15. concentrationconcentrate

Sources & evidence

ORD record
ord-1c79f633092247a59e84f53978ea0418
Source dataset
uspto-grants-2007_10
Patent number
US07276516B2

Reaction notes

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