(R)-2-Aminooctane

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

Procedure: (2S,4S)-1-[[N-(4-carboxybicyclo[2.2.2]oct-1-yl)amino]acetyl]-4-fluoropyrrolidine-2-carbonitrile (50.0 mg) was suspended in dichloromethane (1 mL). To the suspension, trichloroacetonitrile (31.0 μL) and triphenylphosphine (81.1 mg) in dichloromethane (0.5 mL) were added and the mixture was stirred at room temperature for 2 hours. Subsequently, (piperidinomethyl)polystyrene (150 mg) and (2R)-2-aminooctane (57.1 μL) were sequentially added at 0° C. and the mixture was stirred at room temperature for 21 hours. This was followed by addition of (isocyanatomethyl)polystyrene (232 mg), stirring at room temperature for 1 hour, addition of water (3 mL) and dichloromethane (2 mL), and further stirring at room temperature for 50 minutes. The reaction mixture was then loaded onto an Isolute HM-N column and was extracted 5 times with 2 ml dichloromethane. The dichloromethane extracts were combined and concentrated under reduced pressure. The resulting residue was purified by silica gel column (eluant:dichloromethane:methanol=50:1) to give (2S,4S)-4-fluoro-1-[[N-[4-[(2R)—N-(2-octyl)amino]carbonylbicyclo[2.2.2]oct-1-yl]amino]acetyl]pyrrolidine-2-carbonitrile (30.3 mg). the mixture was stirred at room temperature for 21 hours stirring at room temperature for 1 hour further stirring at room temperature for 50 minutes was extracted 5 times with 2 ml dichloromethane concentrated under reduced pressure The resulting residue was purified by silica gel column (eluant:dichloromethane:methanol=50:1)

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

Procedure: (2S,4S)-1-[[N-(4-carboxybicyclo[2.2.2]oct-1-yl)amino]acetyl]-4-fluoropyrrolidine-2-carbonitrile (50.0 mg) was suspended in dichloromethane (1 mL). To the suspension, trichloroacetonitrile (31.0 μL) and triphenylphosphine (81.1 mg) in dichloromethane (0.5 mL) were added and the mixture was stirred at room temperature for 2 hours. Subsequently, (piperidinomethyl)polystyrene (150 mg) and (2R)-2-aminooctane (57.1 μL) were sequentially added at 0° C. and the mixture was stirred at room temperature for 21 hours. This was followed by addition of (isocyanatomethyl)polystyrene (232 mg), stirring at room temperature for 1 hour, addition of water (3 mL) and dichloromethane (2 mL), and further stirring at room temperature for 50 minutes. The reaction mixture was then loaded onto an Isolute HM-N column and was extracted 5 times with 2 ml dichloromethane. The dichloromethane extracts were combined and concentrated under reduced pressure. The resulting residue was purified by silica gel column (eluant:dichloromethane:methanol=50:1) to give (2S,4S)-4-fluoro-1-[[N-[4-[(2R)—N-(2-octyl)amino]carbonylbicyclo[2.2.2]oct-1-yl]amino]acetyl]pyrrolidine-2-carbonitrile (30.3 mg). the mixture was stirred at room temperature for 21 hours stirring at room temperature for 1 hour further stirring at room temperature for 50 minutes was extracted 5 times with 2 ml dichloromethane concentrated under reduced pressure The resulting residue was purified by silica gel column (eluant:dichloromethane:methanol=50:1)

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

Procedure: (2S,4S)-1-[[N-(4-carboxybicyclo[2.2.2]oct-1-yl)amino]acetyl]-4-fluoropyrrolidine-2-carbonitrile (50.0 mg) was suspended in dichloromethane (1 mL). To the suspension, trichloroacetonitrile (31.0 μL) and triphenylphosphine (81.1 mg) in dichloromethane (0.5 mL) were added and the mixture was stirred at room temperature for 2 hours. Subsequently, (piperidinomethyl)polystyrene (150 mg) and (2R)-2-aminooctane (57.1 μL) were sequentially added at 0° C. and the mixture was stirred at room temperature for 21 hours. This was followed by addition of (isocyanatomethyl)polystyrene (232 mg), stirring at room temperature for 1 hour, addition of water (3 mL) and dichloromethane (2 mL), and further stirring at room temperature for 50 minutes. The reaction mixture was then loaded onto an Isolute HM-N column and was extracted 5 times with 2 ml dichloromethane. The dichloromethane extracts were combined and concentrated under reduced pressure. The resulting residue was purified by silica gel column (eluant:dichloromethane:methanol=50:1) to give (2S,4S)-4-fluoro-1-[[N-[4-[(2R)—N-(2-octyl)amino]carbonylbicyclo[2.2.2]oct-1-yl]amino]acetyl]pyrrolidine-2-carbonitrile (30.3 mg). the mixture was stirred at room temperature for 21 hours stirring at room temperature for 1 hour further stirring at room temperature for 50 minutes was extracted 5 times with 2 ml dichloromethane concentrated under reduced pressure The resulting residue was purified by silica gel column (eluant:dichloromethane:methanol=50:1)