Method for preparing alkali salts of p-methylaminobenzoylglutamic acid

Claim 1

AN IMPROVED METHOD FOR PREPARING AN ALKALI SALT OF PMETHYLAMINOBENZOYLGLUTAMIC ACID COMPRISING (1) REACTING AND AQUEOUS MIXTURE OF P-NITRO, OR P-CHLOROBENZOYL CHLORIDE AND A SALT OF GLUTAMIC ACID UNDER ALKALINE CONDITIONS AT A TEMPERATURE OF 20* TO 40*C TO PRODUCE THE CORRESPONDING ALKALI SALT OF P-CHLOROBENZOYLGLUTAMIC ACID, (2) ACIDIFYING THE REACTION MIXTURE TO PRECIPITATE P-NITRO OR P-CHLOROBENZOYLGLUTAMIC ACID, (3) SEPARATING THE LATTER COMPOUND BY FILTRATION, (4) REACTING SAID P-NITRO, OR P-CHLOROBENZOYLGLUTAMIC ACID WITH AN AQUEOUS SOLUTION CONTAINING AN EXCESS OF METHYLAMINE AND CUPROUS CHLORIDE AT A TEMPERAURE OF FROM 115*C TO 150*C IN A CLOSED VESSEL TO OBTAIN A REACTION MIXTURE CONTAINING A SALT OF P-METHYLAMINOBENZLGLUTAMIC ACID, (5) TREATING SAID REACTION MIXTURE WITH AN INORGANIC SULFIDE TO PRECIPITATE THE COPPER AS COPPER SULFIDE, (6) SEPARATING SAID COPPER SULFIDE FROM THE REACTION MIXTURE, (7) TREATING THE REACTION MIXTURE WITH AN ALKALIZING AGENT TO FORM THE ALKALI SALT OF P-METHYIXTURE WITH AN ALKALIZING AGENT TO FORM THE ALKALI SAL OF P-METHYLAMINOBENZOYLGLUTAMIC ACID AND (8) RECOVERING SAID COMPOUND THEREFROM.

Claim 3

A method for preparing an alkali salt of p-methylaminobenzoylglutamic acid comprising (1) reacting an aqueous mixture of one mole of p-nitro, or p-chlorobenzoyl chloride and from about 1.05 to about 1.15 moles of a salt of glutamic acid at an alkaline pH and a temperature from about 20*C. to about 40*C. for a period from about 1 to about 5 hours to obtain a salt of p-chlorobenzoylglutamic acid, (2) acidifying to a pH of about 3, (3) separating the resulting precipitated p-nitro, or p-chloro benzoylglutamic acid by filtration, (4) reacting an aqueous mixture of about one mole of said p-nitro, or p-chlorobenzoylglutamic acid with about 5 to about 15 moles of methylamine and from about 0.2 to about 0.8 mole of cuprous chloride at a temperature from about 115* to about 150*C. for a period from about 5 to about 10 hours to obtain a salt of p-methylaminobenzoylglutamic acid, (5) treating the reaction mixture with an inorganic sulfide to precipitate copper sulfide, (6) separating the copper sulfide therefrom by filtration, (7) treating the resulting filtrate with an alkalizing agent to obtain an alkali p-methylaminobenzoylglutamate, (8) concentrating the reaction mixture to remove excess methylamine, (9) admixing said concentrate with an alcohol to precipitate the alkali p-methylaminobenzoylglutamate and (10) recovering said compound by filtration.

Claim 4

A method for preparing an alkali salt of p-methylaminobenzoylglutamic acid comprising (1) reacting an aqueous mixture of one mole of p-nitro, or p-chlorobenzoyl chloride and from about 1.05 to about 1.15 moles of a salt of glutamic acid at an alkaline pH and a temperature from about 20*C. to about 40*C. for a period from about 1 to about 5 hours to obtain a salt of p-chlorobenzoylglutamic acid, (2) acidifying to a pH of about 3, (3) separating the resulting precipitated p-nitro, or p-chloro benzoylglutamic acid by filtration, (4) reacting an aqueous mixture of about one mole of said p-nitro, or p-chlorobenzoylglutamic acid with about 5 to about 15 moles of methylamine and from about 0.2 to about 0.8 mole of cuprous chloride at a temperature from about 115* to about 150*C. for a period from about 5 to about 10 hours to obtain a salt of p-methylaminobenzoylglutamic acid, (5) treating the reaction mixture with an inorganic sulfide to precipitate copper sulfide, (6) separating the copper sulfide therefrom by filtration, (7) treating the resulting filtrate with an alkalizing agent to obtain an alkali p-methylaminobenzoylglutamate, (8) concentrating the reaction mixture to remove excess methylamine, (9) admixing said concentrate with an alcohol to precipitate the alkali p-methylaminobenzoylglutamate and (10) recovering said compound by filtration.