Methyl 4-cyano-2-fluorobenzoate → Methyl 4-(aminomethyl)-2-fluorobenzoate

HRID 911628Notes

Reaction equation

HRID 911628 reaction equation
[C:1]([C:3]1[CH:12]=[CH:11][C:6]([C:7]([O:9][CH3:10])=[O:8])=[C:5]([F:13])[CH:4]=1)#[N:2]>C(O)C.C(O)(=O)C.O.[Pd]>[NH2:2][CH2:1][C:3]1[CH:12]=[CH:11][C:6]([C:7]([O:9][CH3:10])=[O:8])=[C:5]([F:13])[CH:4]=1

Participants

6

Reactant 1

HCID 15278726Methyl 4-cyano-2-fluorobenzoate

Product 1

HCID 57572260Methyl 4-(aminomethyl)-2-fluorobenzoateYield 59%

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalystHCID 176Acetic AcidSolventHCID 702EthanolSolventHCID 962WaterSolvent

Procedure

Combine a solution of methyl 4-cyano-2-fluoro-benzoate (1 g, 5.58 mmol) in absolute ethanol (42 mL) and acetic acid (1.9 mL) with a mixture of 10% Pd/C (Degussa type E101, 0.17 g, 0.078 mmol) in water (15.6 mL) at room temperature under nitrogen. Purge with nitrogen and then with hydrogen at 55 psi and stir for 1 h. Purge the reaction with nitrogen, filter through Celite® and wash the filter cake with ethanol (100 mL), THF (100 mL) and isopropanol (100 mL). Concentrate in vacuo and purify by SCX chromatography and then chromatography on silica gel (40 g RediSep® column) eluting with dichloromethane/2M ammonia in methanol (99:1 to 9:1 gradient over 30 min; 35 mL/min) to afford the desired intermediate as a white solid (0.602 g, 59%).

Workup

  1. customPurge with nitrogen
  2. customPurge
  3. customthe reaction with nitrogen
  4. filtrationfilter through Celite®
  5. washwash the filter cake with ethanol (100 mL), THF (100 mL) and isopropanol (100 mL)
  6. concentrationConcentrate in vacuo
  7. custompurify by SCX chromatography
  8. washchromatography on silica gel (40 g RediSep® column) eluting with dichloromethane/2M ammonia in methanol (99:1 to 9:1 gradient over 30 min; 35 mL/min)

Sources & evidence

ORD record
ord-b91aa744385a49ab9cb548960eba3105
Source dataset
uspto-grants-2011_09
Patent number
US08022062B2

Reaction notes

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