Production of amoxicillin
AssigneeBristol-Myers Company
InventorsJoseph H. Grossman, Glenn A. Hardcastle, Jr.
Life of this patent
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Abstract
In the production of amoxicillin by acylation of silylated 6-aminopenicillanic acid with the appropriate acid chloride hydrochloride the efficiency of the process and the purity of the product are increased by a new recovery process consisting of isolation from the acylation reaction mixture of solid amoxicillin hydrochloride which is then easily converted to amoxicillin trihydrate.
Claims15
In the process for the production of amoxicillin trihydrate which comprises the consecutive steps of
- a. silylating 6-aminopenicillanic acid in an anhydrous solvent in the presence of a strong base,
- b. acylating said silylated 6-aminopenicillanic acid with D-(-)-2-para-hydroxyphenylglycine chloride hydrochloride in the presence of a weak base and its hydrochloride,
- c. hydrolyzing and neutralizing the product of said acylation to produce amoxicillin trihydrate and
- d. recovering the amoxicillin trihydrate
- the improvement which comprises mixing the products of the acylation reaction of step (b) with water at a highly acidic pH below 2 to form and precipitate solid amoxicillin hydrochloride and then collecting said solid amoxicillin hydrochloride and converting it to amoxicillin trihydrate.
In the process for the production of amoxicillin trihydrate which comprises the consecutive steps of
- a. silylating 6-aminopenicillanic acid in an anhydrous solvent in the presence of a strong base,
- b. acylating said silylated 6-aminopenicillanic acid with D-(-)-2-para-hydroxyphenylglycine chloride hydrochloride in the presence of a weak base and its hydrochloride,
- c. hydrolyzing and neutralizing the product of said acylation to produce amoxicillin trihydrate and
- d. recovering the amoxicillin trihydrate
- the improvement which comprises mixing the products of the acylation reaction of step b) with a volume of water which is about one-half the volume of the acylation reaction mixture at a pH below 2 and then adding NaCl in an amount by weight of about 20 percent of the weight of the water used for hydrolysis to form and precipitate solid amoxicillin hydrochloride and then collecting said solid amoxicillin hydrochloride and converting it to amoxicillin trihydrate.
In the process for the production of amoxicillin trihydrate which comprises the consecutive steps of
- a. silylating 6-aminopenicillanic acid with chlorotrimethylsilane or hexamethyldisilazane in methylene chloride in the presence of triethylamine,
- b. by acylating said silylated 6-aminopenicillanic acid with D-(-)-2-para-hydroxyphenylglycine chloride hydrochloride in the presence of dimethylaniline and its hydrochloride,
- c. hydrolyzing and neutralizing the product of said acylation to produce amoxicillin trihydrate and
- d. recovering the amoxicillin trihydrate
- the improvement of which comprises mixing the products of the acylation reaction of step b) with a volume of water which is about one-half the volume of the acylation reaction mixture at a pH below 2 and then adding NaCl in an amount by weight of about 20 percent of the weight of the water used for hydrolysis to form and precipitate solid amoxicillin hydrochloride and then collecting said solid amoxicillin hydrochloride and converting it to amoxicillin trihydrate.
Dependencies are inferred from the claim text.