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US 6,294,690 B1Granted
Process for preparing a cyclic amino acid anticonvulsant compound
AssigneeWarner-Lambert Company
InventorsCarl Francis Deering, Kenneth Earl Mennen, Robert Ramage
Life of this patent
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Abstract
An improved process for the preparation of a cyclic amino acid by a novel synthesis is described where benzonitrile is treated with an alkali metal and an amine under Birch reduction conditions to generate in situ an anionic intermediate which is alkylated with an α-haloacetic acid moiety which is subsequently converted to the desired product, as well as valuable intermediates used in the process.
Claims49
A process for the preparation of the compound of Formula I
- which comprises:
- treating either the compound of Formula IVb
- or the compound of Formula IVc
- with hydrogen in the presence of a catalyst and a solvent to afford the compound of Formula I.
1 more element
A process for the preparation of the compound of Formula I
- which comprises:
- Step (a) treating the compound of Formula VII
- with an alkali metal in ammonia or higher order amine in the presence of a solvent to afford in situ the compound of Formula VI
- Step (b) treating the compound of Formula VI with a compound of Formula V
- wherein X is halo or sulfonate and R is hydrogen, an alkali metal, an alkaline earth metal, ammonium, an amine cation, alkyl, or benzyl in the presence of a solvent to afford a compound of Formula IV
- wherein R is as defined above;
- Step (c) treating a compound of Formula IVa
- wherein R1a is alkyl with hydrogen in the presence of a catalyst and a solvent to afford a compound of Formula III
- wherein R1a is as defined above;
- Step (d) treating the compound of Formula IIIa
- with an acid in a solvent to afford the compound of Formula II
- or treating a compound of Formula IIIb
- wherein R1b is alkyl excluding tertiary butyl with an acid or base in a solvent to afford the compound of Formula II or treating the compound of Formula IVb
- with hydrogen in the presence of a catalyst and a solvent to afford the compound of Formula II or treating the compound of Formula IVc
- with hydrogen in the presence of a catalyst and a solvent to afford the compound of Formula II;
- Step (e) treating the compound of Formula IVa-1
- with an acid in a solvent to afford the compound of Formula IVb or treating a compound of Formula IVa-2
- wherein R1a-2 is alkyl excluding tertiary butyl with an acid or base in a solvent to afford the compound of Formula IVb;
- and
- Step (f) treating either the compound of Formula IVb or the compound of Formula IVc or the compound of Formula II with hydrogen in the presence of a catalyst and a solvent to afford the compound of Formula I.
17 more elements
A process for the preparation of a compound of Formula III
- wherein R1a is alkyl which comprises:
- Step (a) treating the compound of Formula VII
- with an alkali metal in ammonia or higher order amine in the presence of a solvent to afford in situ the compound of Formula VI
- Step (b) treating the compound of Formula VI with a compound of Formula V
- wherein X is halo or sulfonate and R is hydrogen, an alkali metal, an alkaline earth metal, ammonium, an amine cation, alkyl, or benzyl in the presence of a solvent to afford a compound of Formula IV
- wherein R is as defined above;
- and
- Step (c) treating a compound of Formula IVa
- wherein R1a is alkyl with hydrogen in the presence of a catalyst and a solvent to afford a compound of Formula III.
6 more elements
A process for the preparation of the compound of Formula II
- which comprises:
- Step (a) treating the compound of Formula VII
- with an alkali metal in ammonia or higher order amine in the presence of a solvent to afford in situ the compound of Formula VI
- Step (b) treating the compound of Formula VI with a compound of Formula V
- wherein X is halo or sulfonate and R is hydrogen, an alkali metal, an alkaline earth metal, ammonium, an amine cation, alkyl, or benzyl in the presence of a solvent to afford a compound of Formula IV
- wherein R is as defined above;
- Step (c) treating a compound of Formula IVa
- wherein R1a is alkyl with hydrogen in the presence of a catalyst and a solvent to afford a compound of Formula III
- wherein R1a is as defined above;
- and
- Step (d) treating the compound of Formula IIIa
- with an acid in a solvent to afford the compound of Formula II or treating a compound of Formula IIIb
- wherein R1b is alkyl excluding tertiary butyl with an acid or base in a solvent to afford the compound of Formula II or treating the compound of Formula IVb
- with hydrogen in the presence of a catalyst and a solvent to afford the compound of Formula II or treating the compound of Formula IVc
- with hydrogen in the presence of a catalyst and a solvent to afford the compound of Formula II.
12 more elements
A process for the preparation of the compound of Formula I
- which comprises:
- Step (a) treating the compound of Formula VII
- with an alkali metal in ammonia or higher order amine in the presence of a solvent to afford in situ the compound of Formula VI
- Step (b) treating the compound of Formula VI with a compound of Formula VIII
- wherein X is halo or sulfonate and R2 is alkyl in the presence of a solvent to afford a compound of Formula IX
- wherein R2 is alkyl;
- Step (c) treating a compound of Formula IX with hydrogen in the presence of a catalyst and a solvent to afford a compound of Formula X
- wherein R2 is as defined above;
- Step (d) treating a compound of Formula IX with an acid in the presence of a solvent to afford the compound of Formula IVb
- or treating a compound of Formula X with an acid in the presence of a solvent to afford the compound of Formula II
- Step (e) treating either the compound of Formula IVb or Formula II with hydrogen in the presence of a catalyst and a solvent to afford the compound of Formula I.
8 more elements
A process for the preparation of the compound of Formula II
- which comprises:
- Step (a) treating the compound of Formula VII
- with an alkali metal in ammonia or higher order amine in the presence of a solvent to afford in situ the compound of Formula VI
- Step (b) treating the compound of Formula VI with a compound of Formula VIII
- wherein X is halo or sulfonate and R2 is alkyl in the presence of a solvent to afford a compound of Formula IX
- wherein R2 is alkyl;
- Step (c) treating a compound of Formula IX with hydrogen in the presence of a catalyst and a solvent to afford a compound of Formula X
- wherein R2 is as defined above;
- and
- Step (d) treating a compound of Formula X with an acid in the presence of a solvent to afford the compound of Formula II.
7 more elements
Dependencies are inferred from the claim text.