Glutaric acid derivatives and preparation thereof

Claim 2

The substantially optically pure 2(S)-stereoisomeric form of a compound of the formula:- or a salt thereof, wherein R is C₁-C₄ alkyl or -CH₂CH₂Si(CH₃)₃ and * indicates the asymmetric centre having (S) stereochemistry.

Claim 3

The substantially optically pure 2(S)- stereoisomeric form of a compound of the formula:- or a salt thereof, where R and * are as defined in claim 1.

Claim 4

A process for the preparation of the substantially optically pure 2(S)- stereoisomeric form of a compound of the formula:- or a salt thereof, wherein R is C₁-C₄ alkyl or -CH₂CH₂Si(CH₃)₃ and * indicates the asymmetric centre having (S)- stereochemistry, which comprises reacting a compound of the formula:- wherein R is as defined for a compound of the formula (I), with a salt of the formula:- wherein M¹ and M², which may be the same or different, are selected from Li ⊕ , Na ⊕ and K ⊕ , in an aprotic organic solvent at a temperature at or below -10°C, followed by acidification of the reaction mixture at a temperature at or below -10°C: said process optionally being followed by conversion of the product into a salt thereof.

Claim 5

A process for the preparation of the substantially optically pure 2(S)- stereoisomeric form of a compound of the formula:- or a salt thereof, wherein R is C₁-C₄ alkyl or -CH₂CH₂Si(CH₃)₃ and * indicates the asymmetric centre having (S)- stereochemistry, which comprises reacting a compound of the formula:- wherein R is as defined for a compound of the formula (I), with a salt of the formula:- wherein M¹ and M², which may be the same or different, are selected from Li ⊕ , Na ⊕ and K ⊕ , in an aprotic organic solvent at a temperature at or below -10°C, followed by acidification of the reaction mixture at a temperature at or below -10°C: said process optionally being followed by conversion of the product into a salt thereof.

Claim 6

A process for the preparation of the substantially optically pure 2(S)- stereoisomeric form of a compound of the formula:- or a salt thereof, wherein R is C₁-C₄ alkyl or -CH₂CH₂Si(CH₃)₃ and * indicates the asymmetric centre having (S)- stereochemistry, which comprises (a) reacting a compound of the formula:- wherein R is as defined for a compound of the formula (II), with a salt of the formula:- wherein M¹ and M², which may be the same or different, are selected from Li ⊕ , Na ⊕ and K ⊕ , in an aprotic organic solvent at a temperature at or below -10°C, acidification of the reaction mixture at a temperature at or below -10°C, and optionally followed by conversion of the product into a salt thereof to provide the substantially optically pure 2(S)- stereoisomeric form of a compound of the formula:- or a salt thereof, wherein R and * are as defined for a compound of the formula (II); and (b) catalytic hydrogenation of the product of part (a): said process optionally being followed by conversion of the product of part (b) into a salt thereof to provide the substantially optically pure 2(S)- stereoisomeric form of a compound of the formula (II), or a salt thereof.

Claim 7

A process for the preparation of the substantially optically pure 2(S)- stereoisomeric form of a compound of the formula:- or a salt thereof, wherein R is C₁-C₄ alkyl or -CH₂CH₂Si(CH₃)₃ and * indicates the asymmetric centre having (S)- stereochemistry, which comprises (a) reacting a compound of the formula:- wherein R is as defined for a compound of the formula (II), with a salt of the formula:- wherein M¹ and M², which may be the same or different, are selected from Li ⊕ , Na ⊕ and K ⊕ , in an aprotic organic solvent at a temperature at or below -10°C, acidification of the reaction mixture at a temperature at or below -10°C, and optionally followed by conversion of the product into a salt thereof to provide the substantially optically pure 2(S)- stereoisomeric form of a compound of the formula:- or a salt thereof, wherein R and * are as defined for a compound of the formula (II); and (b) catalytic hydrogenation of the product of part (a): said process optionally being followed by conversion of the product of part (b) into a salt thereof to provide the substantially optically pure 2(S)- stereoisomeric form of a compound of the formula (II), or a salt thereof.

Claim 8

A process for the preparation of the substantially optically pure 2(S)- stereoisomeric form of a compound of the formula (II), or a salt thereof, as defined in claim 4, which comprises catalytic hydrogenation of the substantially optically pure 2(S)- stereoisomeric form of a compound of the formula (I), or a salt thereof, as defined in claim 4: said process optionally being followed by conversion of the product into a salt thereof.

Claim 9

A process as claimed in claim 3 or 4 wherein M¹ and M² are both Li ⊕ .

Claim 10

A process as claimed in claim 6 wherein the salt of the formula (IV) is generated by deprotonation of cyclopentanecarboxylic acid with lithium diisopropylamide and the aprotic organic solvent is tetrahydrofuran.

Claim 11

A process as claimed in claim 4 or 5 in which the catalytic hydrogenation is carried out using a base salt of a compound of the formula (I).

Claim 12

A process as claimed in claim 4, 5 or 8 in which the catalytic hydrogenation is carried out using palladium hydroxide-on-charcoal as the catalyst.

Claim 13

A compound of the formula (III) as defined in claim 3 or 4.

Claim 14

A compound as claimed in claim 1, 2 or 10, or a process as claimed in any one of claims 3 to 9, wherein R is C₁-C₄ alkyl.

Claim 15

A compound as claimed in claim 1, 2, 10 or 11, or a process as claimed in any one of claims 3 to 9 or 11 wherein the salt of a compound of the formula (I) or (II) is an acid addition salt or, preferably, a base salt thereof.