Ammonium formate → Methyl 3-amino-5-fluoro-4-methylbenzoate

HRID 869804Notes

Reaction equation

HRID 869804 reaction equation
[CH3:1][O:2][C:3](=[O:16])[C:4]1[CH:9]=[C:8]([F:10])[C:7]([CH3:11])=[C:6]([N+:12]([O-])=O)[C:5]=1Cl.C([O-])=O.[NH4+]>C(O)C.[Pd]>[CH3:1][O:2][C:3](=[O:16])[C:4]1[CH:9]=[C:8]([F:10])[C:7]([CH3:11])=[C:6]([NH2:12])[CH:5]=1

Participants

5

Reactant 2

HCID 2723923Ammonium formateHCID 866615862-Chloro-5-fluoro-4-methyl-3-nitro-benzoic acid methyl ester

Product 1

HCID 47002571Methyl 3-amino-5-fluoro-4-methylbenzoateYield 88.5%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Conditions

Temperature
75 °C

Procedure

2-Chloro-5-fluoro-4-methyl-3-nitro-benzoic acid methyl ester (Preparation 1d, 53 g), 5% Pd/C (9 g) and ammonium formate (80 g) were stirred together in ethanol (500 mL) at 75° C. for 32 h. The reaction was filtered through celite and filtrate evaporated to a solid. This solid residue was dissolved in dichloromethane, washed with water. The separated aqueous layer was further extracted with dichloromethane (3×100 mL) and the combined organics dried (MgSO4) and evaporated. Analysis showed significant unreacted starting material. The reaction was repeated by new 5% P/C (9 g) and ammonium formate (80 g) together in ethanol (500 mL) and heating at 75° C. for 20 h. Further 5% Pd/C (9 g) and ammonium formate (80 g) were added and heating continued for 10 h. The mixture was filtered through celite and the filter cake was washed with further ethanol. The combined filtrates were evaporated, the residue dissolved in dichloromethane, washed with water. The separated aqueous layer was further extracted with dichloromethane (3×100 mL) and the combined organics dried (MgSO4) and evaporated to afford the subtitle compound (34.7 g).

Workup

  1. filtrationThe reaction was filtered through celite and filtrate
  2. customevaporated to a solid
  3. dissolutionThis solid residue was dissolved in dichloromethane
  4. washwashed with water
  5. extractionThe separated aqueous layer was further extracted with dichloromethane (3×100 mL)
  6. dry with materialthe combined organics dried (MgSO4)
  7. customevaporated
  8. additionFurther 5% Pd/C (9 g) and ammonium formate (80 g) were added
  9. temperatureheating
  10. filtrationThe mixture was filtered through celite
  11. washthe filter cake was washed with further ethanol
  12. customThe combined filtrates were evaporated
  13. dissolutionthe residue dissolved in dichloromethane
  14. washwashed with water
  15. extractionThe separated aqueous layer was further extracted with dichloromethane (3×100 mL)
  16. dry with materialthe combined organics dried (MgSO4)
  17. customevaporated

Sources & evidence

ORD record
ord-6f8d7e673bb54ab2a6a8abda307f1ebb
Source dataset
uspto-grants-2015_03
Patent number
US08969350B2

Reaction notes

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