Hydrochloric Acid → Methyl 3-amino-5-[(4-fluorophenyl)methyl]pyridine-2-carboxylate

HRID 2364195Notes

Reaction equation

HRID 2364195 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]2[CH:10]=[C:11]([N+:19]([O-])=O)[C:12]([C:15]([O:17][CH3:18])=[O:16])=[N:13][CH:14]=2)=[CH:4][CH:3]=1.Cl>C1COCC1.CO.[Pd]>[NH2:19][C:11]1[C:12]([C:15]([O:17][CH3:18])=[O:16])=[N:13][CH:14]=[C:9]([CH2:8][C:5]2[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=2)[CH:10]=1

Participants

6

Reactant 2

HCID 313Hydrochloric AcidHCID 58882963HCID 58882963, compound

Product 1

HCID 58882991Methyl 3-amino-5-[(4-fluorophenyl)methyl]pyridine-2-carboxylate

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalyst2×HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of methyl 5-[(4-fluorophenyl)methyl]-3-nitro-2-pyridinecarboxylate (200 g, 0.66 mol) and Degussa 10% Pd on carbon (50% by weight water, 20 g) in THF (1.5 L) was stirred under an atmosphere of H2 for 2 d. The mixture was filtered through celite and the filtrate was re-subjected to similar hydrogenation conditions with 10% Pd on carbon (30 g) at 45° C. for 7 d. During this time, conc. HCl (14 mL, 0.17 mol) in MeOH (75 mL) and 10% Pd on carbon (18 g) were added in approximately three portions each. The mixture was filtered through celite, concentrated at reduced pressure, reconstituted in CH2Cl2 and washed with saturated NaHCO3 solution. The organic phase was concentrated and the resulting material was triturated with EtOAc to provide the product as an off-white solid: 1H NMR (CDCl3) δ 7.94 (1H, d, J=1.5 Hz), 7.11 (2H, m), 6.98 (2H, m), 6.72 (1H, 1.5 Hz), 5.67 (2H, br s), 3.95 (3H, s), 3.89 (2H, s); ES+ MS: 261 (M+H+, 100).

Workup

  1. filtrationThe mixture was filtered through celite
  2. waitthe filtrate was re-subjected to similar hydrogenation conditions with 10% Pd on carbon (30 g) at 45° C. for 7 d
  3. filtrationThe mixture was filtered through celite
  4. concentrationconcentrated at reduced pressure
  5. washwashed with saturated NaHCO3 solution
  6. concentrationThe organic phase was concentrated
  7. customthe resulting material was triturated with EtOAc

Sources & evidence

ORD record
ord-fa739973cbb741c5918233350ad8da88
Source dataset
uspto-grants-2014_04
Patent number
US08691991B2

Reaction notes

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