Oxopyrrolidine compounds, preparation of said compounds and their use in the manufacturing of Levetiracetam and analogues

1. A process for the manufacture of an S isomer of a compound of formula (8)

wherein

R 1 is methyl or ethyl; and

R 2 is C 2 -C 4 alkyl, C 2 -C 4 alkenyl or C 2 -C 4 alkynyl, optionally substituted by one or more halogen; said process comprising the following steps:

(a) reacting a compound of formula (9)

with an alcohol of formula R 1 OH, wherein R 1 is as defined for the compound of formula (8), and thionyl chloride, to obtain a compound of formula (10),

(b) reacting the compound of formula (10) with a R 2 -substituted-ethyl-4-bromobutyrate, wherein R 2 is as defined for the compound of formula (8), to obtain a compound of formula (11),

(c) cyclisation of the compound of formula (11) with a catalyst, and

(d) isolating the S isomer of the compound of formula (8).

2. The process according claim 1 , wherein step (b) is performed in the presence of a base and an alcohol.

3. The process according to claim 1 , wherein the catalyst used in step (c) is pyridinol.

4. A process for the manufacture of an S isomer of a compound of formula (8)

wherein

R 1 is methyl or ethyl; and

R 2 is C 2 -C 4 alkyl, C 2 -C 4 alkenyl or C 2 -C 4 alkynyl, optionally substituted by one or more halogen, said process comprising a step of cyclisation of a compound of the formula (11)

wherein R 1 and R 2 are as defined for the compound of formula (8).

5. A process for the manufacture of an S isomer of a compound of formula (8)

wherein

R 1 is methyl or ethyl; and

R 2 is C 2 -C 4 alkyl, C 2 -C 4 alkenyl or C 2 -C 4 alkynyl, optionally substituted by one or more halogen, said process comprising the following steps:

(a) reacting an α-ketocarboxylic acid derivative of formula (12),

wherein R 1 is as defined for the compound of formula (8), with a pyrrolidinone of formula (13),

wherein R 2 is as defined for the compound of formula (8), to obtain a compound of formula (14),

(b) reacting the compound of formula (14) with hydrogen in the presence of an asymmetric hydrogenation catalyst, and

(c) isolating the S isomer of the compound of formula (8).

6. A process for the manufacture of an S isomer of a compound of formula (8)

wherein

R 1 is methyl or ethyl; and

R 2 is C 2 -C 4 alkyl, C 2 -C 4 alkenyl or C 2 -C 4 alkynyl, optionally substituted by one or more halogen, said process comprising the following steps:

(a) reacting a compound of formula (15),

wherein R 1 is C 1 -C 6 alkyl and X is Cl, Br, I, alkylsuiphonate or sulfate, with a pyrrolidone of formula (13),

wherein R 2 is as defined for the compound of formula (8), to obtain a compound of formula (16),

(b) reacting the compound of formula (16) with ethyl-X, wherein X is Cl, Br, I, alkylsulphonate or sulfate, in the presence of an asymmetric alkylation catalyst or additive,

(c) optionally, when R 1 ′ is different from R 1 , reacting the compound obtained in step (b) with an alcohol of formula R 1 OH, and

(d) isolating the S isomer of the compound of formula (8).

7. A process for the manufacture of an S isomer of a compound of formula (8),

wherein

R 1 is methyl or ethyl; and

R 2 is C 2 -C 4 alkyl, C 2 -C 4 alkenyl or C 2 -C 4 alkynyl, optionally substituted by one or more halogen, said process comprising the following steps:

(a) reacting a compound of general formula (20),

wherein R 1 is as defined for the compound of formula (8), with a pyrrolidone of general formula (13),

wherein R 2 is defined as for the compound of formula (8), to obtain a compound of formula (21),

wherein R 1 and R 2 are defined as for the compound of formula (8),

(b) separating the compound of formula (21), and

(c) isolating the S isomer of the compound of formula (8).