Process for the preparation and isolation of the individual stereoisomers of 1-amino, 3-substituted phenylcyclopentane-carboxylates

A process for isolating the compound of Formula 2b

• wherein R is Br or methoxy, comprising the steps of forming a salt with L-tartaric acid and separating the diastereomeric salt mixture based on differential solubility in a solvent.

A process for the preparation of a compound of Formula 3 comprising the steps of reacting a compound of Formula 2b

• with aqueous HCl and dioxane until the reaction is substantially complete to isolate a compound of Formula 3
• wherein R is Br or methoxy.

A process for preparing a compound of Formula 4

• comprising the steps of reacting a compound of Formula 3
• with methanol and thionyl chloride until the reaction is substantially complete to form a compound of Formula 4
• wherein R is Br or methoxy.

A process for preparing a compound of Formula 5

• comprising the steps of reacting a substituted arylboronic acid and a rhodium catalyst with (R)- or (S)-BINAP in an organic solvent, water that is degassed with nitrogen and adding a cyloalkanone of the formula
• until the reaction is substantially complete to form a compound of Formula 5
• wherein R is Br or methoxy.

A process for the preparation of a mixture of compounds of Formula 6a and Formula 6b

• comprising the steps of reacting a mixture of ammonium carbonate and a cyanide salt in water with a compound of Formula 5
• wherein R is Br, until the reaction is substantially complete to give a mixture of compound of Formula 6a and Formula 6b

A process for the preparation of a mixture of compounds of Formula 7a and Formula 7b

• comprising the steps of reacting the mixture of compounds of Formula 6a and Formula 6b
• with potassium carbonate and an alkylating agent until the reaction is substantially complete to give a mixture of compounds of Formula 7a and Formula 7b

A process for isolating a compound of Formula 8

• comprising the steps of dissolving the mixture of compounds of Formula 7a and Formula 7b
• in hot acetonitrile and then cooling the solution until the reaction is substantially complete to give a compound of Formula 8

A process for the preparation of a compound of Formula 9

• comprising the steps of hydrolizing Formula 8
• with an aqueous base until the reaction is substantially complete to give a compound of Formula 9

A process for preparing a mixture of compounds of Formula 10a and Formula 10b

• comprising treating the mixture of compounds of Formula 6a and 6b
• with an inorganic base until the reaction is substantially complete to form a mixture of compounds of Formula 10a and 10b

A process for preparing a mixture of compounds of Formula 11a and Formula 11b

• comprising reacting the mixture of compounds of Formula 10a and Formula 10b
• with thionyl chloride and methanol until the reaction is substantially complete to form a mixture of compounds of Formula 11a and Formula 11b

A process of isolating a compound of Formula 11a

• comprising the step of filtering the mixture of compounds of Formula 11a and Formula 11b
• to isolate a compound of Formula 11a