4-methylpiperidine-3-carboxylic acid

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

Procedure: Hydrogen chloride gas was bubbled into a solution of 4-methylpiperidine-3-carboxylic acid (6.0 g, 41.90 mmol) in ethanol (150 mL) and acetic acid (30 mL) at 0° C. under a nitrogen atmosphere. The reaction mixture was heated at reflux for 48 h, then was cooled and was partitioned between water and ethyl acetate. The organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure to afford ethyl 4-methylpiperidine-3-carboxylate (5.0 g). The material was used without further purification. The reaction mixture was heated at reflux for 48 h was cooled was partitioned between water and ethyl acetate The organic layer was dried over sodium sulfate filtered concentrated under reduced pressure

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

Procedure: 4-Methylnicotinic acid (5.0 g, 36.46 mmol) in acetic acid (40 mL) was added to a wet solution of platinum oxide (500 mg) under a nitrogen atmosphere. The suspension was hydrogenated under a hydrogen atmosphere (200 PSI) at room temperature for 18 h. The mixture was filtered through a pad of Celite under nitrogen and the filtrate was concentrated under reduced pressure to afford 4-methylpiperidine-3-carboxylic acid (6.0 g). The material was used without further purification. at room temperature for 18 h The mixture was filtered through a pad of Celite under nitrogen the filtrate was concentrated under reduced pressure

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

Procedure: 4-Methylnicotinic acid (5.0 g, 36.46 mmol) in acetic acid (40 mL) was added to a wet solution of platinum oxide (500 mg) under a nitrogen atmosphere. The suspension was hydrogenated under a hydrogen atmosphere (200 PSI) at room temperature for 18 h. The mixture was filtered through a pad of Celite under nitrogen and the filtrate was concentrated under reduced pressure to afford 4-methylpiperidine-3-carboxylic acid (6.0 g). The material was used without further purification. at room temperature for 18 h The mixture was filtered through a pad of Celite under nitrogen the filtrate was concentrated under reduced pressure

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

Procedure: AcOH (380 mL) was added to 4-methylnicotinic acid hydrochloride (50.5 g, 291 mmol, Maybridge) and PtO2 (5.05 g, 22.2 mmol, Johnson Matthey) in a 600 mL stainless steel reactor. The mixture was stirred under 220 psi of hydrogen at ambient temperature for about 14 hr. The supernatant solution was filtered through a nylon membrane and rinsed with enough AcOH until only the catalyst remained. The filtrate was concd under reduced pressure to give a clear oil that solidified upon cooling to ambient temperature to give crude 4-methylpiperidine-3-carboxylic acid with AcOH as an excipient (88.94 g, 170%): LC/MS (Table 1, Method b) Rt=0.44 min; MS m/z: 144 (M+H)+. The supernatant solution was filtered through a nylon membrane rinsed with enough AcOH until only the catalyst to give a clear oil that

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

Procedure: AcOH (380 mL) was added to 4-methylnicotinic acid hydrochloride (50.5 g, 291 mmol, Maybridge) and PtO2 (5.05 g, 22.2 mmol, Johnson Matthey) in a 600 mL stainless steel reactor. The mixture was stirred under 220 psi of hydrogen at ambient temperature for about 14 hr. The supernatant solution was filtered through a nylon membrane and rinsed with enough AcOH until only the catalyst remained. The filtrate was concd under reduced pressure to give a clear oil that solidified upon cooling to ambient temperature to give crude 4-methylpiperidine-3-carboxylic acid with AcOH as an excipient (88.94 g, 170% crude): LC/MS (Table 1, Method b) Rt=0.44 min; MS m/z: 144 (M+H)+. The supernatant solution was filtered through a nylon membrane rinsed with enough AcOH until only the catalyst to give a clear oil that

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

Procedure: Hydrogen chloride gas was bubbled into a solution of 4-methylpiperidine-3-carboxylic acid (6.0 g, 41.90 mmol) in ethanol (150 mL) and acetic acid (30 mL) at 0° C. under a nitrogen atmosphere. The reaction mixture was heated at reflux for 48 h, then was cooled and was partitioned between water and ethyl acetate. The organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure to afford ethyl 4-methylpiperidine-3-carboxylate (5.0 g). The material was used without further purification. The reaction mixture was heated at reflux for 48 h was cooled was partitioned between water and ethyl acetate The organic layer was dried over sodium sulfate filtered concentrated under reduced pressure

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

Procedure: 4-Methylnicotinic acid (5.0 g, 36.46 mmol) in acetic acid (40 mL) was added to a wet solution of platinum oxide (500 mg) under a nitrogen atmosphere. The suspension was hydrogenated under a hydrogen atmosphere (200 PSI) at room temperature for 18 h. The mixture was filtered through a pad of Celite under nitrogen and the filtrate was concentrated under reduced pressure to afford 4-methylpiperidine-3-carboxylic acid (6.0 g). The material was used without further purification. at room temperature for 18 h The mixture was filtered through a pad of Celite under nitrogen the filtrate was concentrated under reduced pressure