Reaction #52994

Reaction equation

4-Chlorobutyryl chloride

DIEA

4-amino-2-chlorobenzoic acid methyl ester hydrochloride

DIEA

4-chlorobutyryl chloride

→

4-(4-chlorobutyryl)amino-2-chlorobenzoic acid methyl ester

Solvents

CH2Cl2

CH2Cl2

Conditions

Workup

1. 1
   workup.STIRRINGthe mixture was stirred at room temperature overnight
2. 2
   workup.STIRRINGthe mixture was stirred for 24 h
3. 3
   Washthe solution was washed successively with 1N HCl, std
4. 4
   DryingNaHCO3, brine, dried
5. 5
   Otherevaporated
6. 6
   OtherThe residue was purified by column chromatography (silica gel; eluent: hexane/EtOAc 3:1)

Procedure

To a solution of 4-amino-2-chlorobenzoic acid methyl ester hydrochloride (0.52 g) and DIEA (0.27 mL) in CH2Cl2 (20 mL) at 0° C. under N2 was added 4-chlorobutyryl chloride (0.3 mL) and the mixture was stirred for 4 h at that temperature. DMAP (0.23 mmol) was added and the mixture was stirred at room temperature overnight. 4-Chlorobutyryl chloride (0.3 mL) and DIEA (0.09 mL) were added and the mixture was stirred for 24 h. The mixture was diluted with CH2Cl2 (100 mL) and the solution was washed successively with 1N HCl, std. NaHCO3, brine, dried and evaporated. The residue was purified by column chromatography (silica gel; eluent: hexane/EtOAc 3:1) to yield 4-(4-chlorobutyryl)amino-2-chlorobenzoic acid methyl ester (0.64 g). ESMS: m/z 290 (MH+).

Source