Acetic Acid → 1-(4-Amino-2-fluoro-phenyl)-2,3-dihydro-1H-pyridin-4-one

HRID 2213360

Reaction equation

HRID 2213360 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([N+:8]([O-])=O)[CH:5]=[CH:4][C:3]=1[N:11]1[CH:16]=[CH:15][C:14](=[O:17])[CH2:13][CH2:12]1.C(O)(=O)C.[H][H]>C1COCC1.[Pd].C([O-])([O-])=O.[Ca+2]>[NH2:8][C:6]1[CH:5]=[CH:4][C:3]([N:11]2[CH:12]=[CH:13][C:14](=[O:17])[CH2:15][CH2:16]2)=[C:2]([F:1])[CH:7]=1

Participants

6

Reactant 3

HCID 176Acetic AcidHCID 218776411-(2-fluoro-4-nitrophenyl)-2,3-dihydro-1H-pyridin-4-oneHCID 178418361HCID 178418361, compound

Product 1

HCID 218778771-(4-Amino-2-fluoro-phenyl)-2,3-dihydro-1H-pyridin-4-one

Reagents, catalysts & solvents 2

HCID 12000666Calcium Palladium CarbonateCatalystHCID 8028TetrahydrofuranSolvent

Procedure

In a 500 ml Parr bottle, the nitrophenyl compound from step 3 (35 g, 148.3 mmol), Pd/CaCO3 (3.5 g, 10 wt %) and acetic acid (17 ml, 297 mmol) are combined in THF (350 ml). The mixture is hydrogenated at 40° C. under 15 psi hydrogen for 6 h at which time the reaction is complete by HPLC. The reaction mixture is filtered through a GF/F filter and the catalyst cake washed with THF (350 ml). The filtrate is partitioned between 500 ml of NaHCO3 and 500 ml of ethyl acetate. The organic layer is washed again with 500 ml of NaHCO3. The organic layer is separated and dried over MgSO4. The mixture is filtered, and the filtrated is concentrated in vacuo to afford 29.0 g (95% recovery) of crude title compound. MS (ESI−) for C11H11FN2O m/z 205.0 (M−H)−; 1H NMR (MeOD) δ 7.37 (d, J=7.5, 1 H), 7.02 (t, J=9.0, 1 H), 6.47 (m, 3 H), 5.07 (d, J=7.4, 1 H), 3.84 (t, J=7.8, 2 H), 2.58 (t, J=7.8, 1 H); 13C NMR (MeOD) δ 195.1, 160.1, 157.7, 157.1, 151.2, 127.9, 124.0, 122.9, 112.2, 103.5, 103.2, 100.2, 51.4, 36.8.

Workup

  1. filtrationThe reaction mixture is filtered through a GF/F
  2. filtrationfilter
  3. washthe catalyst cake washed with THF (350 ml)
  4. customThe filtrate is partitioned between 500 ml of NaHCO3 and 500 ml of ethyl acetate
  5. washThe organic layer is washed again with 500 ml of NaHCO3
  6. customThe organic layer is separated
  7. dry with materialdried over MgSO4
  8. filtrationThe mixture is filtered
  9. concentrationthe filtrated is concentrated in vacuo

Sources & evidence

ORD record
ord-60ace992023c4108ab5ac2343d4c5d52
Source dataset
uspto-grants-2006_09
Patent number
US07105547B2

Linked notes

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