2,5-dimethylcyclopentan-1-one

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A process for the preparation of the compounds of the present invention which are substituted by alkyl substituents, e.g., methyl substituents in the 8 and/or 11 positions, begins with the treatment of an α,α-dihaloxylene with an alkylated or dialkylated derivative of the appropriate cycloalkanone-enamine. Thus, for example, α,α-dibromoxylene is treated with the pyrrolidine enamine of 2,5-dimethylcyclopentanone to produce the corresponding 6,9-dimethyl-5,6,7,8,9,10-hexahydro-6,9-methanobenzocyclooctene-11-one, followed by thallation as described hereinabove, to introduce the corresponding 2'-hydroxy compound and subsequent conversion to the oxime, followed by catalytic reduction to the desired d,1-11-endo-amino-6,9-dimethyl-5,6,7,8,9,10-hexahydro-6,9-methanobenzocyclooctene. A process for the preparation of the compounds of the present invention which

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A process for the preparation of the compounds of the present invention which are substituted by alkyl substituents, e.g., methyl substituents in the 8 and/or 11 positions, begins with the treatment of an α,α-dihaloxylene with an alkylated or dialkylated derivative of the appropriate cycloalkanone-enamine. Thus, for example, α,α-dibromoxylene is treated with the pyrrolidine enamine of 2,5-dimethylcyclopentanone to produce the corresponding 6,9-dimethyl-5,6,7,8,9,10-hexahydro-6,9-methanobenzocyclooctene-11-one, followed by thallation as described hereinabove, to introduce the corresponding 2'-hydroxy compound and subsequent conversion to the oxime, followed by catalytic reduction to the desired d,1-11-endo-amino-6,9-dimethyl-5,6,7,8,9,10-hexahydro-6,9-methanobenzocyclooctene. A process for the preparation of the compounds of the present invention which

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A process for the preparation of the compounds of the present invention which are substituted by alkyl substituents, e.g., methyl substituents in the 8 and/or 11 positions, begins with the treatment of an α,α-dihaloxylene with an alkylated or dialkylated derivative of the appropriate cycloalkanone-enamine. Thus, for example, α,α-dibromoxylene is treated with the pyrrolidine enamine of 2,5-dimethylcyclopentanone to produce the corresponding 6,9-dimethyl-5,6,7,8,9,10-hexahydro-6,9-methanobenzocyclooctene-11-one, followed by thallation as described hereinabove, to introduce the corresponding 2'-hydroxy compound and subsequent conversion to the oxime, followed by catalytic reduction to the desired d,1-11-endo-amino-6,9-dimethyl-5,6,7,8,9,10-hexahydro-6,9-methanobenzocyclooctene. A process for the preparation of the compounds of the present invention which

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: α,α'-Dibromoxylene (30.3 g., 0.115 Mole) is dissolved in dry acetonitrile (250 ml.) and then, under nitrogen, the pyrrolidine enamine of 2,5-dimethylcyclopentanone (prepared from 2,5-dimethylcyclopentanone and pyrrolidine via the method of Stork) is added dropwise over one-half hour. The mixture is refluxed 2 days, cooled, water (100 ml.) is added; and the mixture is refluxed 1 hour, cooled, concentrated in vacuo, then extracted with ether (3×75 ml.). The combined extracts are washed with 10% HCl (50 ml.), brine (50 ml.), then dried and evaporated to yield 16 g. of solid, which recrystallized from dichloroethane-hexane gives pure title compound (9.7 g.). The mother liquors are chromatographed on silica gel (100 g.), eluting with ether-hexane (1:4) to give 5.8 g. more title compound, which yields 4.9 g. pure on crystallization from ether-hexane (64% total yield), m.p. 134°-135° C. is added dropwise over one-half hour The mixture is refluxed 2 days cooled and the mixture is refluxed 1 hour cooled concentrated in vacuo extracted with ether (3×75 ml.) The combined extracts are washed with 10% HCl (50 ml.), brine (50 ml.) dried evaporated to yield 16 g of solid, which recrystallized from dichloroethane-hexane

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A process for the preparation of the compounds of the present invention which are substituted by alkyl substituents, e.g., methyl substitutents in the 6 and/or 9 positions, begins with the treatment of an α,α-dihaloxylene with an alkylated or dialkylated derivative of the appropriate cycloalkanone-enamine. Thus, for example, α,α-dibromoxylene is treated with the pyrrolidine enamine of 2,5 -dimethylcyclopentanone to produce the corresponding 6,9-dimethyl-5,6,7,8,9,10-hexahydro-6,9-methanobenzocyclooctene-11-one, followed by thallation as described hereinabove, to introduce the corresponding 2'-hydroxy compound and subsequent conversion to the oxime, followed by catalytic reduction to the desired d,l-11- endo-amine-6,9-dimethyl-5,6,7,8,9,10-hexahydro-6,9-methanobenzocyclooctene. A process for the preparation of the compounds of the present invention which

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A process for the preparation of the compounds of the present invention which are substituted by alkyl substituents, e.g., methyl substituents in the 8 and/or 11 positions, begins with the treatment of an α,α-dihaloxylene with an alkylated or dialkylated derivative of the appropriate cycloalkanone-enamine. Thus, for example, α,α-dibromoxylene is treated with the pyrrolidine enamine of 2,5-dimethylcyclopentanone to produce the corresponding 6,9-dimethyl-5,6,7,8,9,10-hexahydro-6,9-methanobenzocyclooctene-11-one, followed by thallation as described hereinabove, to introduce the corresponding 2'-hydroxy compound and subsequent conversion to the oxime, followed by catalytic reduction to the desired d,1-11-endo-amino-6,9-dimethyl-5,6,7,8,9,10-hexahydro-6,9-methanobenzocyclooctene. A process for the preparation of the compounds of the present invention which

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A process for the preparation of the compounds of the present invention which are substituted by alkyl substituents, e.g., methyl substituents in the 6 and/or 9 positions, begins with the treatment of an α,α-dihaloxylene with an alkylated or dialkylated derivative of the appropriate cycloalkanone-enamine. Thus, for example, α,α-dibromoxylene is treated with the pyrrolidine enamine of 2,5-dimethylcyclopentanone to produce the corresponding 6,9-dimethyl-5,6,7,8,9,10-hexahydro-6,9-methanobenzocyclooctene-11-one, followed by thallation as described hereinabove, to introduce the corresponding 2'-hydroxy compound and subsequent conversion to the oxime, followed by catalytic reduction to the desired D,L-11-endo-amino-6,9-dimethyl-5,6,7,8,9,10-hexahydro-6,9-methanobenzocyclooctene. A process for the preparation of the compounds of the present invention which

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A process for the preparation of the compounds of the present invention which are substituted by alkyl substituents, e.g., methyl substituents in the 8 and/or 11 positions, begins with the treatment of an α,α-dihaloxylene with an alkylated or dialkylated derivative of the appropriate cycloalkanone-enamine. Thus, for example, α,α-dibromoxylene is treated with the pyrrolidine enamine of 2,5-dimethylcyclopentanone to produce the corresponding 6,9-dimethyl-5,6,7,8,9,10-hexahydro-6,9-methanobenzocyclooctene-11-one, followed by thallation as described hereinabove, to introduce the corresponding 2'-hydroxy compound and subsequent conversion to the oxime, followed by catalytic reduction to the desired d,1-11-endo-amino-6,9-dimethyl-5,6,7,8,9,10-hexahydro-6,9-methanobenzocyclooctene. A process for the preparation of the compounds of the present invention which