Hydrochloric Acid → Ethyl 5-(aminomethyl)-2-(difluoromethyl)nicotinate hydrochloride

HRID 241429Notes

Reaction equation

HRID 241429 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([C:12]([O:14][CH3:15])=[O:13])[C:6]([CH:9]([F:11])[F:10])=[N:7][CH:8]=1)#[N:2].[ClH:16].[H][H].[CH3:19]CO>[Pd]>[ClH:16].[NH2:2][CH2:1][C:3]1[CH:4]=[C:5]([C:12]([O:14][CH2:15][CH3:19])=[O:13])[C:6]([CH:9]([F:11])[F:10])=[N:7][CH:8]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 702Ethanol2×HCID 71059861Methyl 5-cyano-2-(difluoromethyl)pyridine-3-carboxylateHCID 178418361HCID 178418361, compound

Product 1

HCID 71059730Ethyl 5-(aminomethyl)-2-(difluoromethyl)nicotinate hydrochlorideYield 96%

Reagents, catalysts & solvents 1

HCID 23938PalladiumCatalyst

Procedure

Purge a mixture of methyl 5-cyano-2-(difluoromethyl)pyridine-3-carboxylate (160 g, 707.4 mmol) and EtOH (2 L) with nitrogen and stir 15 min. Add hydrochloric acid (37 wt % aqueous, 273 mL, 3183.2 mmol, 4.5 equiv) and palladium (5% on carbon, 48 g, 22.5 mmol, 0.031 equiv) in EtOH (100 mL), and stir the resulting suspension under 60 psi of hydrogen at room temperature for 70 min. Remove the solids by filtration over diatomaceous earth; wash the solid cake with EtOH (1 L); and concentrate the filtrate under reduced pressure. Repeat this procedure twice; combine the solids; and slurry in Et2O:DCM [10:1, 5.5 L]. Filter the solids and dry the resulting material at 45° C. for 3 hours to give the title compound as a light brown solid (714 g, 96% yield). MS (m/z) 216 (M+1).

Workup

  1. customPurge
  2. customRemove the solids
  3. filtrationby filtration over diatomaceous earth
  4. washwash the solid cake with EtOH (1 L)
  5. concentrationand concentrate the filtrate under reduced pressure
  6. filtrationFilter the solids
  7. customdry the resulting material at 45° C. for 3 hours

Sources & evidence

ORD record
ord-48caa241a0a04d9cbcad565a5864bc9b
Source dataset
uspto-grants-2014_02
Patent number
US08648200B2

Reaction notes

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