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US 6,673,926 B2Granted
Process of preparing 3S-3-amino-3-aryl proprionic acid and derivatives thereof
AssigneeOrtho-McNeil Pharmaceutical, Inc.
InventorsLorraine Scott, Frank John Villani, Jr., Donald G. Walker
Life of this patent
Estimating the term…
Abstract
The present invention is directed to a process for preparing 3S-3-amino-3-aryl propionic acid and derivatives thereof.
Claims24
A process of preparing the compound of formula
- wherein
- R1 is pyrimidyl optionally substituted with one or two substituents selected independently from the group consisting of halogen, alkyl, alkoxy, aralkyl, —NR32, wherein R3 is alkyl and R4 CONH wherein R4 is phenyl or alkyl, or pyridyl optionally substituted with one or two substituents selected independently from the group consisting of halogen, alkyl, alkoxy, aralkyl, —NR32, wherein R3 is alkyl and R4 CONH wherein R4 is phenyl or alkyl and R2 is hydrogen, alkyl or aralkyl, or acid addition salts thereof,
- comprising reacting a compound of formula II, at a pH range of between about 7 and about 11,
- to form a compound of formula III
- wherein R5 is N-t-butoxycarbonyl,
- reacting a compound of formula III with at least 0.5 equivalents of (1R,2S)-(−)ephedrine, in an alkyl acetate solvent, to form a salt of formula IV
- wherein Ph is phenyl,
- reacting the salt of formula IV with an inorganic base in water to form a carboxylate salt of the compound of formula V, acidifying the carboxylate salt of the compound of formula V with an acid of pKa less than or equal to three, to a pH of between about 3.5 and about 6.5, to form the compound of formula V
- reacting the compound of formula V, at a temperature less than about 25° C., to form the compound of formula I.
6 more elements
A process of preparing a compound of formula I
- wherein
- R1 is pyrimidyl optionally substituted with one or two substituents selected independently from the group consisting of halogen, alkyl, alkoxy, aralkyl, —NR32, wherein R3 is alkyl and R4CONH wherein R4 is phenyl or alkyl, or pyridyl optionally substituted with one or two substituents selected independently from the group consisting of halogen, alkyl, alkoxy, aralkyl, —NR32, wherein R3 is alkyl and R4CONH wherein R4 is phenyl or alkyl and R2 is hydrogen, alkyl or aralkyl, or acid addition salts thereof,
- comprising reacting a compound of formula III
- with at least 0.5 equivalents of (1R,2S)-(−)ephedrine, in alkyl acetate solvent, to form a salt of formula IV
- wherein Ph is phenyl,
- reacting the salt of formula IV with an inorganic base, in water, to form a carboxylate salt of the compound of formula V, acidifying the carboxylate salt of the compound of formula V with an acid of pKa less than or equal to three, to a pH of between about 3.5 and about 6.5, to form the compound of formula V
- reacting the compound of formula V, at a temperature less than about 25° C. to form the compound of formula I.
4 more elements
Dependencies are inferred from the claim text.