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

HRID 1807260Notes

Reaction equation

HRID 1807260 reaction equation
[C:1]([C:3]1[CH:11]=[CH:10][C:6]([C:7]([OH:9])=[O:8])=[C:5]([O:12][CH3:13])[CH:4]=1)#[N:2].O.[C:15]1(C)C=CC(S(O)(=O)=O)=CC=1>CO>[CH3:15][O:8][C:7](=[O:9])[C:6]1[CH:10]=[CH:11][C:3]([C:1]#[N:2])=[CH:4][C:5]=1[O:12][CH3:13]

Participants

4

Reactant 2

HCID 521998p-Toluenesulfonic acid monohydrateHCID 151660044-Cyano-2-methoxybenzoic acid

Product 1

HCID 57426183Methyl 4-cyano-2-methoxybenzoateYield 367.8%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of 4-cyano-2-methoxy benzoic acid (1.0 g, 5.65 mmol, Biogene) in methanol was reacted with p-toluenesulfonic acid monohydrate (285.6 mg, 1.479 mmol) and heated to reflux for 16 hrs. The solvent was removed and the reaction residue was extracted with EtOAc, and washed with saturated sodium carbonate, water, and saturated NaCl, and dried over Na2SO4 to give 4-Cyano-2-methoxy-benzoic acid methyl ester (1.04 g, 96%). This ester (1.01 g, 5.28 mmol) in methanol (50 mL) was reacted with Raney Ni (3 spatula tips full, exact amount unknown, Aldrich) under 50 psi H2 in a Parr apparatus for 16 hrs. After filtering through Celite and concentrating, the crude mixture was purified by silica gel chromatography using methanol and methylene chloride to give 4-aminomethyl-2-methoxy-benzoic acid methyl ester (385.7 mg, 37%).

Workup

  1. temperatureheated
  2. temperatureto reflux for 16 hrs
  3. customThe solvent was removed
  4. extractionthe reaction residue was extracted with EtOAc
  5. washwashed with saturated sodium carbonate, water, and saturated NaCl
  6. dry with materialdried over Na2SO4

Sources & evidence

ORD record
ord-584a2a7083af4124b3742acbab614677
Source dataset
uspto-grants-2013_01
Patent number
US08354444B2

Reaction notes

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