Reaction #436673

Reaction equation

NaHCO3

p-toluene sulfonic acid

3-amino-4-methoxy benzoic acid methyl ester

2-chloro-4-fluorobenzonitrile

→

title compound

Yield 72.0%

3-[(2-chloro-4-fluoro-benzimidoyl)-amino]-4-methoxy-benzoic acid methyl ester

Yield 72.0%

Conditions

Workup

1. 1
   workup.ADDITIONwere added
2. 2
   TemperatureThe resulting solution was cooled to room temperature
3. 3
   ExtractionThe resulting mixture was extracted with ethyl acetate
4. 4
   Dryingthe extract was dried over MgSO4
5. 5
   Concentrationconcentrated under a reduced pressure
6. 6
   OtherThe resulting residue was purified by silica gel column chromatography

Procedure

Anhydrous p-toluene sulfonic acid (41.99 g, 220.76 mmol) was melted at 120° C. and 3-amino-4-methoxy benzoic acid methyl ester (20 g, 110.38 mmol) obtained in step 1 of Preparation Example 1 and 2-chloro-4-fluorobenzonitrile (25.76 g, 165.57 mol) were added thereto and stirred at 160° C. for 8 hours. The resulting solution was cooled to room temperature and the reaction was stopped by adding NaHCO3 thereto. The resulting mixture was extracted with ethyl acetate, the extract was dried over MgSO4 and concentrated under a reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain the title compound (26.70 g, 79.47 mmol) in a yield of 72%.

Source