Originator
Colazal,Salix Pharmaceuticals,,USA
Manufacturing Process
125 g finely powdered 4-nitrobenzoyl chloride were added portionwise, while
stirring, to a solution of 70 g β-alanine in 500 ml water containing 65 g
sodium hydroxide and cooled to 5°C. The reaction mixture was stirred for 3
hours and then added to a mixture of ice and hydrochloric acid. The
precipitate obtained was filtered off, washed with water and dried by suction.
After crystallisation of the dried product from hot acetone, there were
obtained 130 g 4-nitrobenzoyl-β-alanine, M.P. 164°-166°C.
A suspension of 15 g finely powdered 4-nitrobenzoyl-β-alanine in 200 ml
ethanol was stirred in an atmosphere of hydrogen in the presence of 1 g of
palladium-charcoal (5%), while cooling gently. When the absorption of
hydrogen had ceased, the reaction mixture was filtered and the filtrate
concentrated to a small volume. Upon adding diethyl ether and cooling 4-
aminobenzoyl-β-alanine was obtained. The yield was 11.5 g, M.P. 156°-158°C.
8.8 g 4-aminobenzoyl-β-alanine were triturated with 12 ml hydrochloric acid
and the paste obtained was dissolved in 100 ml water. The solution was
cooled to -5°C and a solution of 3 g sodium nitrite in 20 ml water, cooled to
0°C, was added dropwise, while stirring. The diazotised solution was left for 1
hour at 0°C and was then added dropwise at -5°C to a solution of 6 g salicylic
acid in 70 ml water containing 3.6 g sodium hydroxide and 7 g sodium
carbonate. The final reaction mixture was adjusted to a pH of about 8, stirred
for 2 to 3 hours and added to a mixture of dilute hydrochloric acid and ice.
The precipitate obtained was filtered off, washed with water and suction dried.
Crystallisation from hot ethanol gave 11.9 g 5-[(2-carboxy-ethylcarbamoyl)-
phenylazo]-2-hydroxy-benzoic acid, M.P. 254°-255°C.
10.7 g of the free acid were dissolved in 300 ml warm ethanol and treated
with a solution of 2.4 g sodium hydroxide in 25 ml ethanol. The precipitate
obtained was filtered off, washed with ethanol and diethyl ether and dried in a
vacuum at 50°C to give 11.5 g of the disodium salt of 5-[(2-carboxyethylcarbamoyl)-
phenylazo]-2-hydroxy-benzoic acid, M.P. >350°C.
