p-Toluenesulfonic acid monohydrate → Methyl 4-cyano-2-fluorobenzoate

HRID 1807264Notes

Reaction equation

HRID 1807264 reaction equation
[C:1]([C:3]1[CH:11]=[CH:10][C:6]([C:7]([OH:9])=[O:8])=[C:5]([F:12])[CH:4]=1)#[N:2].O.[C:14]1(C)C=CC(S(O)(=O)=O)=CC=1>CO>[C:1]([C:3]1[CH:11]=[CH:10][C:6]([C:7]([O:9][CH3:14])=[O:8])=[C:5]([F:12])[CH:4]=1)#[N:2]

Participants

4

Reactant 2

HCID 521998p-Toluenesulfonic acid monohydrateHCID 5906594-Cyano-2-fluorobenzoic acid

Product 1

HCID 15278726Methyl 4-cyano-2-fluorobenzoateYield 1,024.5%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of 4-cyano-2-fluorobenzoic acid (4.02 g, 24.36 mmol, Aldrich) in methanol (50 mL) was treated with p-toluenesulfonic acid monohydrate (0.46 g, 2.43 mmol) and heated to reflux overnight. The solvent was removed and the reaction residue was extracted with EtOAc, washed with saturated Na2CO3, brine and dried over Na2SO4 to give Methyl 4-cyano-2-fluorobenzoate (4.46 g, 95%). This Methyl ester (1.03 g, 5.77 mmol) was combined with methanol (60 mL) and Raney Ni (2 spatula tip fulls were added after washing with methanol under argon). It was then put under Hydrogen at 50 PSI on a PARR shaker for 18 hrs. The reaction was filtered through celite and washed with methanol while being kept under N2. It was then purified by silica gel chromatography with methanol and methylene chloride to give methyl 4-(aminomethyl)-2-fluorobenzoate (247.6 mg, 23%) as off-white solid.

Workup

  1. temperatureheated
  2. temperatureto reflux overnight
  3. customThe solvent was removed
  4. extractionthe reaction residue was extracted with EtOAc
  5. washwashed with saturated Na2CO3, brine
  6. dry with materialdried over Na2SO4

Sources & evidence

ORD record
ord-7a26e843528b4fd095fb660fe3a459a7
Source dataset
uspto-grants-2013_01
Patent number
US08354444B2

Reaction notes

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