1-methylcyclohexa-1,4-diene

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of benzyl 4-((3-(((tert-butoxycarbonyl)amino)(phenyl)-methyl)phenoxy)methyl)piperidine-1-carboxylate (1.12 g, 2.11 mmol) in ethanol (10 mL), was added 10% palladium on charcoal (0.22 g) and 1-methyl1,4-cyclohexadiene (1.18 mL, 10.55 mmol). The reaction mixture was heated to 80° C. for 7 hours. The reaction mixture was filtered through a pad of celite, and the filter-pad washed with further ethanol. The filtrate was evaporated at reduced pressure to afford the title compound (0.716 g, 85%). The reaction mixture was filtered through a pad of celite the filter-pad washed with further ethanol The filtrate was evaporated at reduced pressure

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1-Methyl-1,4-cyclohexadiene (10.0 mL, 89 mmol) was added to a suspension of (E)-methyl 3-(4-(diethoxymethyl)phenyl)acrylate (2.41 g, 9.13 mmol) and 10% palladium on carbon (2.4 g) in ethanol (40 mL). The reaction mixture was heated at 60° C. for 1.5 hours. The reaction mixture was filtered through celite and the filter cake washed with further ethanol. The solvent was evaporated at reduced pressure to afford the title compound (2.15 g, 89%). The reaction mixture was filtered through celite the filter cake washed with further ethanol The solvent was evaporated at reduced pressure

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of (R)-5-(2-azido-1-((tert-butyldimethylsilyl)oxy)ethyl)-8-(benzyloxy)quinolin-2(1H)-one (4.50 g, 10.0 mmol) in ethanol (50 mL) was added 10% palladium on charcoal (4.50 g) followed by 1-methyl-1,4-cyclohexadiene (11.0 mL, 97.9 mmol). The reaction was warmed to 60° C. and then stirred at 60° C. for 2 hours. The reaction mixture was allowed to cool and filtered through a pad of celite. The filtercake was washed with further ethanol and the filtrate was evaporated at reduced pressure. The residue was evaporated from iso-propanol (×2) and dissolved in iso-propanol (30 mL). HCl-dioxane (4 M, 50 mL, 200 mmol) was added and the reaction mixture stirred at RT for 18 hours. The resultant suspension was filtered, the filtercake washed with ether and the solid dried under vacuum in the presence of P2O5 to afford the title compound (1.65 g, 62%). to cool filtered through a pad of celite The filtercake was washed with further ethanol the filtrate was evaporated at reduced pressure The residue was evaporated from iso-propanol (×2) dissolved in iso-propanol (30 mL) the reaction mixture stirred at RT for 18 hours The resultant suspension was filtered the filtercake washed with ether the solid dried under vacuum in the presence of P2O5

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of (R)-5-(2-azido-1-((tert-butyldimethylsilyl)oxy)ethyl)-8-(benzyloxy)quinolin-2(1H)-one (4.50 g, 10.0 mmol) in ethanol (50 mL) was added 10% palladium on charcoal (4.50 g) followed by 1-methyl-1,4-cyclohexadiene (11.0 mL, 97.9 mmol). The reaction was warmed to 60° C. and then stirred at 60° C. for 2 hours. The reaction mixture was allowed to cool and filtered through a pad of celite. The filtercake was washed with further ethanol and the filtrate was evaporated at reduced pressure. The residue was evaporated from iso-propanol (×2) and dissolved in iso-propanol (30 mL). HCl-dioxane (4 M, 50 mL, 200 mmol) was added and the reaction mixture stirred at RT for 18 hours. The resultant suspension was filtered, the filtercake washed with ether and the solid dried under vacuum in the presence of P2O5 to afford the title compound (1.65 g, 62%). to cool filtered through a pad of celite The filtercake was washed with further ethanol the filtrate was evaporated at reduced pressure The residue was evaporated from iso-propanol (×2) dissolved in iso-propanol (30 mL) the reaction mixture stirred at RT for 18 hours The resultant suspension was filtered the filtercake washed with ether the solid dried under vacuum in the presence of P2O5

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

Procedure: To a solution of benzyl 4-((3-((S)-phenyl((((R)-quinuclidin-3-yloxy)carbonyl)-amino)methyl)phenoxy)methyl)piperidine-1-carboxylate (1.32 g, 2.26 mmol) in ethanol (100 mL) was added palladium on charcoal (0.66 g) and stirred at room temperature for 10 minutes. 1-Methyl-1,4-cyclohexadiene (1.27 mL, 11.3 mmol) was added and the reaction mixture heated to reflux. The reaction mixture was stirred under reflux for 1 hour. The reaction mixture was allowed to cool and the suspension filtered. The filtrate was evaporated at reduced pressure to afford the title compound (1.05 g, 100%). the reaction mixture heated to reflux The reaction mixture was stirred under reflux for 1 hour to cool the suspension filtered The filtrate was evaporated at reduced pressure

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

Procedure: To a suspension of N-benzylcyclopentanamine hydrochloride (0.986 g, 4.66 mmol) in acetonitrile (10 mL) was added di-iso-propylethylamine (2.0 mL, 11.5 mmol) and the mixture stirred at room temperature for 10 minutes. A solution of 2-(2-bromoethyl)-1,3-dioxolane (1.01 g, 5.58 mmol) in acetonitrile (5 mL) was added and the mixture heated at 80° C. for 48 hours. The reaction mixture was diluted with DCM and was washed with water, dried (magnesium sulfate), filtered and the solvent evaporated at reduced pressure. The residue was loaded onto an SCX-2 cartridge and eluted with acetonitrile (4 column volumes) and then 10% triethylamine/acetonitrile (4 column volumes). The product containing fractions were combined and the solvent evaporated at reduced pressure. The residue was dissolved in ethanol (10 mL) and 10% palladium on charcoal (0.90 g) added. The mixture was stirred at room temperature for 5 minutes and then 1-methyl-1,4-cyclohexadiene (1.9 mL, 16.9 mmol) added. The reaction mixture heated to reflux and then the reaction mixture stirred under reflux for 1 hour. The reaction mixture allowed to cool and the suspension filtered. The filtrate was evaporated at reduced pressure to afford the title compound (0.249 g, 40%). the mixture heated at 80° C. for 48 hours was washed with water dried (magnesium sulfate) filtered the solvent evaporated at reduced pressure eluted with acetonitrile (4 column volumes) The product containing fractions the solvent evaporated at reduced pressure The residue was dissolved in ethanol (10 mL) 10% palladium on charcoal (0.90 g) added The mixture was stirred at room temperature for 5 minutes The reaction mixture heated to reflux the reaction mixture stirred under reflux for 1 hour to cool the suspension filtered The filtrate was evaporated at reduced pressure

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

Procedure: To a stirred solution of N-(2-(1,3-dioxolan-2-yl)ethyl)-N-benzyl-2-((tert-butyldimethylsilyl)oxy)ethanamine (3.87 g, 10.6 mmol) in ethanol (100 mL) was added 10% palladium on carbon (1.93 g) and 1-methyl-1,4-cyclohexadiene (5.93 mL, 53.0 mmol). The suspension was heated at reflux for 30 minutes and allowed to cool. The suspension was filtered through celite and the filter cake washed with further ethanol. The solvent was evaporated at reduced pressure to afford the title compound (2.64 g, 91%). The suspension was heated at reflux for 30 minutes to cool The suspension was filtered through celite the filter cake washed with further ethanol The solvent was evaporated at reduced pressure

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

Procedure: To a stirred solution of N-(2-(1,3-dioxolan-2-yl)ethyl)-N-benzyl-2-((tert-butyldimethylsilyl)oxy)ethanamine (3.87 g, 10.6 mmol) in ethanol (100 mL) was added 10% palladium on carbon (1.93 g) and 1-methyl-1,4-cyclohexadiene (5.93 mL, 53.0 mmol). The suspension was heated at reflux for 30 minutes and allowed to cool. The suspension was filtered through celite and the filter cake washed with further ethanol. The solvent was evaporated at reduced pressure to afford the title compound (2.64 g, 91%). The suspension was heated at reflux for 30 minutes to cool The suspension was filtered through celite the filter cake washed with further ethanol The solvent was evaporated at reduced pressure