The present disclosure is related to an improved and efficient process for preparation of (3R,4R)-(1-benzyl-4-methylpiperidin-3-yl)-methylamine which comprises:

(a) N-acylation of 3-Amino-4-methyl pyridine; (b) Quarternization of 3-Acetylamino-4-methyl pyridine using benzyl halide; (c) Partial reduction of quarternized 3-Acetylamino-4-methyl pyridine by Sodium borohydride in Methanol or water; (d) Hydrolysis of partially reduced product to 1-Benzyl-4-methylpiperidin-3-one in presence of acid; (e) Reductive amination of 1-Benzyl-4-methylpiperidin-3-one using Methanolic methylamine in presence of Titanium(IV) isopropoxide in Methanol; (f) Resolution of 1-Benzyl-4-methylpiperidin-3-yl)-methylamine using Ditoluoyl (L) tartaric acid to get (3R,4R)-(1-benzyl-4-methylpiperidin-3-yl)-methylamine. The disclosure is also related to novel intermediates:

##STR00001##

wherein R, R and X are as described in the specification.

The present invention is related to an improved and efficient process for preparation of (3R,4R)-(1-benzyl-4-methylpiperidin-3-yl)-methylamine which comprises: (a) N-acylation of 3-Amino-4-methyl pyridine; (b) Quarternization of 3-Acetylamino-4-methyl pyridine using benzyl halide; (c) Partial reduction of quarternized 3-Acetylamino-4-methyl pyridine by Sodium borohydride in Methanol or water; (d) Hydrolysis of partially reduced product to 1-Benzyl-4-methylpiperidin-3-one in presence of acid; (e) Reductive amination of 1-Benzyl-4-methylpiperidin-3-one using Methanolic methylamine in presence of Titanium(IV) isopropoxide in Methanol; (f) Resolution of 1-Benzyl-4-methylpiperidin-3-yl)-methylamine using Ditoluoyl (L) tartaric acid to get (3R,4R)-(1-benzyl-4-methylpiperidin-3-yl)-methylamine. The invention is also related to novel intermediates: ##STR00001##
wherein R, R and X are as described in the specification.

The present invention is related to an improved and efficient process for preparation of (3R,4R)-(1-benzyl-4-methylpiperidin-3-yl)-methylamine which comprises: (a) N-acylation of 3-Amino-4-methyl pyridine; (b) Quarternization of 3-Acetylamino-4-methyl pyridine using benzyl halide; (c) Partial reduction of quarternized 3-Acetylamino-4-methyl pyridine by Sodium borohydride in Methanol or water; (d) Hydrolysis of partially reduced product to 1-Benzyl-4-methylpiperidin-3-one in presence of acid; (e) Reductive amination of 1-Benzyl-4-methylpiperidin-3-one using Methanolic methylamine in presence of Titanium(IV) isopropoxide in Methanol; (f) Resolution of 1-Benzyl-4-methylpiperidin-3-yl)-methylamine using Ditoluoyl (L) tartaric acid to get (3R,4R)-(1-benzyl-4-methylpiperidin-3-yl)-methylamine. The invention is also related to novel intermediates: ##STR00001##
wherein R, R and X are as described in the specification.

Disclosed are compounds of Formula I, including all stereoisomers, (N-oxides), and salts thereof, wherein A and R are as defined in the disclosure. ##STR00001## Also disclosed is a method for preparing a compound of Formula I, comprising reacting a compound of Formula II with an aroyl enolate salt of Formula III in the presence of an acid in an aqueous solvent mixture, wherein A, R and M are as defined in the disclosure. Also disclosed is a method for preparing a compound of Formula IV, comprising reacting a compound of Formula I with an aldehyde of Formula V in the presence of a secondary amine salt, wherein A, B and R are as defined in the disclosure ##STR00002##

A method for separating a homogeneous catalyst from a solution includes forming a host-guest compound between a first isomer of the catalyst and inclusion compound in the solution and isolating the host-guest compound from the solution. The catalyst may be released from the inclusion compound by converting the first isomer of the catalyst to a second isomer of the catalyst.

This describes homogeneous catalysts that are recoverable from solution by being phase selective and through host-guest interactions. An example of a method includes separating a water soluble N-heterocyclic carbene homogeneous catalyst from a solution by: (a) forming a host-guest compound between the catalyst and an inclusion compound in the solution; and (b) isolating the host-guest compound from the solution.

This describes homogeneous catalysts that are recoverable from solution by being phase selective and through host-guest interactions. An example of a method includes separating a water soluble N-heterocyclic carbene homogeneous catalyst from a solution by: (a) forming a host-guest compound between the catalyst and an inclusion compound in the solution; and (b) isolating the host-guest compound from the solution.

The present disclosure is related to an improved and efficient process for preparation of (3R,4R)-(1-benzyl-4-methylpiperidin-3-yl)-methylamine which comprises:

(a) N-acylation of 3-Amino-4-methyl pyridine; (b) Quarternization of 3-Acetylamino-4-methyl pyridine using benzyl halide; (c) Partial reduction of quarternized 3-Acetylamino-4-methyl pyridine by Sodium borohydride in Methanol or water; (d) Hydrolysis of partially reduced product to 1-Benzyl-4-methylpiperidin-3-one in presence of acid; (e) Reductive amination of 1-Benzyl-4-methylpiperidin-3-one using Methanolic methylamine in presence of Titanium(IV) isopropoxide in Methanol; (f) Resolution of 1-Benzyl-4-methylpiperidin-3-yl)-methylamine using Ditoluoyl (L) tartaric acid to get (3R,4R)-(1-benzyl-4-methylpiperidin-3-yl)-methylamine. The disclosure is also related to novel intermediates:

##STR00001##

wherein R, R and X are as described in the specification.

A novel process is provided for the efficient preparation of an asymmetric compound of structural formula I:

##STR00001##

employing dynamic kinetic resolution (DKR). The DKR process involves an enzymatic enantioselective amination reaction catalyzed by transaminases. The process can be used to manufacture key intermediates in the preparation of poly (ADP-ribose) polymerase (PARP) inhibitors which may be useful for the treatment of cancer.

A novel process is provided for the efficient preparation of an asymmetric compound of structural formula I:

##STR00001##

employing dynamic kinetic resolution (DKR). The DKR process involves an enzymatic enantioselective amination reaction catalyzed by transaminases. The process can be used to manufacture key intermediates in the preparation of poly (ADP-ribose) polymerase (PARP) inhibitors which may be useful for the treatment of cancer.