Diethyl Malonate → 6-Fluoro-1,3-dihydro-2H-pyrrolo[3,2-b]pyridin-2-one

HRID 2394342Notes

Reaction equation

HRID 2394342 reaction equation
C([O:3][C:4]([CH:6](C(OCC)=O)[C:7]1[C:12]([N+:13]([O-])=O)=[CH:11][C:10]([F:16])=[CH:9][N:8]=1)=O)C.C(OCC)(=O)CC(OCC)=O.NC1C(C(C(OCC)=O)C(OCC)=O)=NC=C(F)C=1>C(O)C.[Ni].O.Cl>[F:16][C:10]1[CH:11]=[C:12]2[C:7]([CH2:6][C:4](=[O:3])[NH:13]2)=[N:8][CH:9]=1

Participants

8

Reactant 3

HCID 7761Diethyl Malonate3×HCID 10614138HCID 10614138, compoundHCID 10825891HCID 10825891, compound2×

Product 1

HCID 106069316-Fluoro-1,3-dihydro-2H-pyrrolo[3,2-b]pyridin-2-one

Reagents, catalysts & solvents 4

HCID 935NickelCatalystHCID 313Hydrochloric AcidSolventHCID 702EthanolSolvent3×HCID 962WaterSolvent

Procedure

The mixture of 2-bis(ethoxycarbonyl)methyl-5-fluoro-3-nitropyridine and diethyl malonate was dissolved in ethanol (100 mL) and added to a suspension of 50% Raney nickel in water (7.8 g) diluted with ethanol (150 mL). The mixture was hydrogenated in a Parr shaker at 3 atmospheres pressure overnight and then filtered through diatomaceous earth (Celite (trademark)) to remove the catalyst. The solvent was removed in vacuo to leave a mixture of 3-amino-2-bis(ethoxycarbonyl)methyl-5-fluoropyridine and diethyl malonate as an oil. The mixture containing 3-amino-2-bis(ethoxycarbonyl)methyl-5-fluropyridine and diethyl malonate was taken up in 6N HCl solution (280 mL) and heated at reflux for 3 hours. After removing the aqueous acid in vacuo, the residue was taken up in water and again concentrated to leave a solid. This was taken up in dry ethanol and concentrated two times to obtain the title compound as a light green solid (4.07 g) which was triturated with hot ethyl acetate and dried in the air. Although somewhat impure by NMR this material was used in directly in the next step without further purification.

Workup

  1. customwas hydrogenated in a Parr shaker at 3 atmospheres pressure overnight
  2. filtrationfiltered through diatomaceous earth (Celite (trademark))
  3. customto remove the catalyst
  4. customThe solvent was removed in vacuo
  5. customto leave
  6. temperatureheated
  7. temperatureat reflux for 3 hours
  8. customAfter removing the aqueous acid in vacuo
  9. concentrationagain concentrated
  10. customto leave a solid
  11. concentrationconcentrated two times

Sources & evidence

ORD record
ord-9218fef6513f4b6e83ab8504eb5a8ed3
Source dataset
uspto-grants-1998_09
Patent number
US05811432

Reaction notes

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