3-piperidin-2-ylpropan-1-ol

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

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

Procedure: 2-(3-Hydroxypropyl)pyridine (5 g, 36.44 mmoles) was dissolved in 1N HCl (36.4 mL, 36.4 mmoles) and water (63.6 mL) and platinum (IV) oxide monohydrate (1 g, 4.08 mmoles) was added under an argon atmosphere. The mixture was hydrogenated at 55 psi in a Parr bomb at 25° C. for 96 h. The catalyst was filtered off through Celite® and washed with water. The combined filtrates were treated with BioRad AG1-X8 (OH−) resin until basic. The resin was filtered off and washed with water. The combined filtrates were evaporated to dryness and the product was chromatographed on silica gel using 10% increasing to 20% (10% conc. NH4OH in methanol)-dichloromethane as the eluant to give the title compound (5.22 g, 100%): CIMS: m/z 144.40 (MH+); δC (d6-DMSO) CH2: 24.0, 25.3, 28.8, 31.5, 32.8, 45.9, 60.8; CH: 56.1. The catalyst was filtered off through Celite® washed with water The combined filtrates were treated with BioRad The resin was filtered off washed with water The combined filtrates were evaporated to dryness the product was chromatographed on silica gel using 10% increasing to 20% (10% conc. NH4OH in methanol)-dichloromethane as the eluant

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

Procedure: 2-(3-Hydroxypropyl)pyridine (5 g, 36.4 mmoles) was dissolved in 1N HCl (36.4 mL, 36.4 mmoles) and water (63.6 mL) and platinum (IV) oxide monohydrate (1 g, 4.08 mmoles) was added under an argon atmosphere. The mixture was hydrogenated at 55 psi in a Parr bomb at 25° C. for 96 h. The catalyst was filtered off through Celite® and washed with water. The combined filtrates were treated with BioRad AG1-X8 (OH) resin until basic. The resin was filtered off and washed with water. The combined filtrates were evaporated to dryness and the product was chromatographed on silica gel using 10% increasing to 20% (10% conc. NH4OH in methanol)dichloromethane as the eluant to give the title compound (5.22 g, 100%): CIMS: m/z 144.40 (MH+); δC (d6-DMSO) CH2: 24.0, 25.3, 28.8, 31.5, 32.8, 45.9, 60.8; CH: 56.1. The catalyst was filtered off through Celite® washed with water The combined filtrates were treated with BioRad The resin was filtered off washed with water The combined filtrates were evaporated to dryness the product was chromatographed on silica gel using 10% increasing to 20% (10% conc. NH4OH in methanol)dichloromethane as the eluant

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

Procedure: 2-(3-Hydroxypropyl)pyridine (5 g, 36.4 mmoles) was dissolved in 1N HCl (36.4 mL, 36.4 mmoles) and water (63.6 mL) and platinum (IV) oxide monohydrate (1 g, 4.08 mmoles) was added under an argon atmosphere. The mixture was hydrogenated at 55 psi in a Parr bomb at 25° C. for 96 h. The catalyst was filtered off through Celite® and washed with water. The combined filtrates were treated with BioRad AG1-X8 (OH) resin until basic. The resin was filtered off and washed with water. The combined filtrates were evaporated to dryness and the product was chromatographed on silica gel using 10% increasing to 20% (10% conc. NH4OH in methanol)dichloromethane as the eluant to give the title compound (5.22 g, 100%): CIMS: m/z 144.40 (MH+); δC (d6-DMSO) CH2: 24.0, 25.3, 28.8, 31.5, 32.8, 45.9, 60.8; CH: 56.1. The catalyst was filtered off through Celite® washed with water The combined filtrates were treated with BioRad The resin was filtered off washed with water The combined filtrates were evaporated to dryness the product was chromatographed on silica gel using 10% increasing to 20% (10% conc. NH4OH in methanol)dichloromethane as the eluant

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

Procedure: 3-(2-Piperidinyl)-1-propanol (8.69 g, 60.7 mmol) was stirred in acetonitrile (90 ml) with triethylamine (10.40 mL, 74.6 mmol) under N2 and cooled in an ice bath. Benzyl chloroformate (9.53 ml, 66.7 mmol) was added dropwise. After complete addition the reaction was allowed to warm to ambient temperature and stirring then continued overnight. The suspension was filtered and the filtrate evaporated to dryness. The residue was partitioned between ethyl acetate and water. The organic phase was washed with saturated brine, passed through a hydrophobic frit and evaporated to dryness. The residue was purified by chromatography on silica (330 g silica RediSep column, loaded in DCM) using a 0-50% ethyl acetate in cyclohexane gradient over 40 mins. with a 50-100% flush of ethyl acetate on an ISCO Companion. No peaks were detected (254 nm, 280 nm) so the waste was evaporated in vacuo to recover the material. The material was re-columned using identical conditions as before but detecting at 220 nm and collecting all the eluent. The main product peak was collected and evaporated in vacuo to give the title compound as a yellow oil (6.15 g). LCMS (System B): tRET=2.46 min; MH+ 278 cooled in an ice bath After complete addition the reaction The suspension was filtered the filtrate evaporated to dryness The residue was partitioned between ethyl acetate and water The organic phase was washed with saturated brine evaporated to dryness The residue was purified by chromatography on silica (330 g silica RediSep column, loaded in DCM) over 40 mins with a 50-100% flush of ethyl acetate on an ISCO Companion was evaporated in vacuo to recover the material collecting all the eluent The main product peak was collected evaporated in vacuo

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

Procedure: 2-(3-Hydroxypropyl)pyridine (5 g, 36.44 mmoles) was dissolved in 1N HCl (36.4 mL, 36.4 mmoles) and water (63.6 mL) and platinum (IV) oxide monohydrate (1 g, 4.08 mmoles) was added under an argon atmosphere. The mixture was hydrogenated at 55 psi in a Parr bomb at 25° C. for 96 h. The catalyst was filtered off through Celite® and washed with water. The combined filtrates were treated with BioRad AG1-X8 (OH−) resin until basic. The resin was filtered off and washed with water. The combined filtrates were evaporated to dryness and the product was chromatographed on silica gel using 10% increasing to 20% (10% conc. NH4OH in methanol)-dichloromethane as the eluant to give the title compound (5.22 g, 100%): CIMS: m/z 144.40 (MH+); δC (d6-DMSO) CH2: 24.0, 25.3, 28.8, 31.5, 32.8, 45.9, 60.8; CH: 56.1. The catalyst was filtered off through Celite® washed with water The combined filtrates were treated with BioRad The resin was filtered off washed with water The combined filtrates were evaporated to dryness the product was chromatographed on silica gel using 10% increasing to 20% (10% conc. NH4OH in methanol)-dichloromethane as the eluant

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

Procedure: 2-(3-Hydroxypropyl)pyridine (5 g, 36.44 mmoles) was dissolved in 1N HCl (36.4 mL, 36.4 mmoles) and water (63.6 mL) and platinum (IV) oxide monohydrate (1 g, 4.08 mmoles) was added under an argon atmosphere. The mixture was hydrogenated at 55 psi in a Parr bomb at 25° C. for 96 h. The catalyst was filtered off through Celite® and washed with water. The combined filtrates were treated with BioRad AG1-X8 (OH−) resin until basic. The resin was filtered off and washed with water. The combined filtrates were evaporated to dryness and the product was chromatographed on silica gel using 10% increasing to 20% (10% conc. NH4OH in methanol)-dichloromethane as the eluant to give the title compound (5.22 g, 100%): CIMS: m/z 144.40 (MH+); δC (d6-DMSO) CH2: 24.0, 25.3, 28.8, 31.5, 32.8, 45.9, 60.8; CH: 56.1. The catalyst was filtered off through Celite® washed with water The combined filtrates were treated with BioRad The resin was filtered off washed with water The combined filtrates were evaporated to dryness the product was chromatographed on silica gel using 10% increasing to 20% (10% conc. NH4OH in methanol)-dichloromethane as the eluant

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

Procedure: 2-(3-Hydroxypropyl)pyridine (5 g, 36.4 mmoles) was dissolved in 1N HCl (36.4 mL, 36.4 mmoles) and water (63.6 mL) and platinum (IV) oxide monohydrate (1 g, 4.08 mmoles) was added under an argon atmosphere. The mixture was hydrogenated at 55 psi in a Parr bomb at 25° C. for 96 h. The catalyst was filtered off through Celite® and washed with water. The combined filtrates were treated with BioRad AG1-X8 (OH) resin until basic. The resin was filtered off and washed with water. The combined filtrates were evaporated to dryness and the product was chromatographed on silica gel using 10% increasing to 20% (10% conc. NH4OH in methanol)dichloromethane as the eluant to give the title compound (5.22 g, 100%): CIMS: m/z 144.40 (MH+); δC (d6-DMSO) CH2: 24.0, 25.3, 28.8, 31.5, 32.8, 45.9, 60.8; CH: 56.1. The catalyst was filtered off through Celite® washed with water The combined filtrates were treated with BioRad The resin was filtered off washed with water The combined filtrates were evaporated to dryness the product was chromatographed on silica gel using 10% increasing to 20% (10% conc. NH4OH in methanol)dichloromethane as the eluant

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

Procedure: 3-(2-Piperidinyl)-1-propanol (8.69 g, 60.7 mmol) was stirred in acetonitrile (90 ml) with triethylamine (10.40 mL, 74.6 mmol) under N2 and cooled in an ice bath. Benzyl chloroformate (9.53 ml, 66.7 mmol) was added dropwise. After complete addition the reaction was allowed to warm to ambient temperature and stirring then continued overnight. The suspension was filtered and the filtrate evaporated to dryness. The residue was partitioned between ethyl acetate and water. The organic phase was washed with saturated brine, passed through a hydrophobic frit and evaporated to dryness. The residue was purified by chromatography on silica (330 g silica RediSep column, loaded in DCM) using a 0-50% ethyl acetate in cyclohexane gradient over 40 mins. with a 50-100% flush of ethyl acetate on an ISCO Companion. No peaks were detected (254 nm, 280 nm) so the waste was evaporated in vacuo to recover the material. The material was re-columned using identical conditions as before but detecting at 220 nm and collecting all the eluent. The main product peak was collected and evaporated in vacuo to give the title compound as a yellow oil (6.15 g). cooled in an ice bath After complete addition the reaction The suspension was filtered the filtrate evaporated to dryness The residue was partitioned between ethyl acetate and water The organic phase was washed with saturated brine evaporated to dryness The residue was purified by chromatography on silica (330 g silica RediSep column, loaded in DCM) over 40 mins with a 50-100% flush of ethyl acetate on an ISCO Companion was evaporated in vacuo to recover the material collecting all the eluent The main product peak was collected evaporated in vacuo

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

Procedure: 3-(2-Piperidinyl)-1-propanol (8.69 g, 60.7 mmol) was stirred in acetonitrile (90 ml) with triethylamine (10.40 mL, 74.6 mmol) under N2 and cooled in an ice bath. Benzyl chloroformate (9.53 ml, 66.7 mmol) was added dropwise. After complete addition the reaction was allowed to warm to ambient temperature and stirring then continued overnight. The suspension was filtered and the filtrate evaporated to dryness. The residue was partitioned between ethyl acetate and water. The organic phase was washed with saturated brine, passed through a hydrophobic frit and evaporated to dryness. The residue was purified by chromatography on silica (330 g silica RediSep column, loaded in DCM) using a 0-50% ethyl acetate in cyclohexane gradient over 40 mins. with a 50-100% flush of ethyl acetate on an ISCO Companion. No peaks were detected (254 nm, 280 nm) so the waste was evaporated in vacuo to recover the material. The material was re-columned using identical conditions as before but detecting at 220 nm and collecting all the eluent. The main product peak was collected and evaporated in vacuo to give the title compound as a yellow oil (6.15 g). cooled in an ice bath After complete addition the reaction The suspension was filtered the filtrate evaporated to dryness The residue was partitioned between ethyl acetate and water The organic phase was washed with saturated brine evaporated to dryness The residue was purified by chromatography on silica (330 g silica RediSep column, loaded in DCM) over 40 mins with a 50-100% flush of ethyl acetate on an ISCO Companion was evaporated in vacuo to recover the material collecting all the eluent The main product peak was collected evaporated in vacuo

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

Procedure: 3-(2-Piperidinyl)-1-propanol (commercially available, for example from ChemBridge Corporation) (8.69 g, 60.7 mmol) was stirred in acetonitrile (90 mL) with triethylamine (10.40 mL, 74.6 mmol) under nitrogen and cooled in an ice bath. Benzyl chloroformate (commercially available, for example, from Aldrich) (9.53 mL, 66.7 mmol) was added dropwise. After complete addition the reaction was allowed to warm to ambient temperature and stirring then continued overnight. The suspension was filtered and the filtrate evaporated to dryness. The residue was partitioned between ethyl acetate and water. The organic phase was washed with saturated brine, passed through a hydrophobic frit and evaporated to dryness. The residue was purified by chromatography on silica (330 g silica RediSep column, loaded in DCM) using a 0-50% ethyl acetate in cyclohexane gradient over 40 minutes with a 50-100% flush of ethyl acetate on an ISCO Companion. No peaks were detected (254 nm, 280 nm) so the waste was evaporated in vacuo to recover the material. The material was re-columned using identical conditions as before but detecting at 220 nm and collecting all the eluent. The main product peak was collected and evaporated in vacuo to give the title compound as a yellow oil (6.15 g). cooled in an ice bath After complete addition the reaction The suspension was filtered the filtrate evaporated to dryness The residue was partitioned between ethyl acetate and water The organic phase was washed with saturated brine evaporated to dryness The residue was purified by chromatography on silica (330 g silica RediSep column, loaded in DCM) over 40 minutes flush of ethyl acetate on an ISCO Companion was evaporated in vacuo to recover the material collecting all the eluent The main product peak was collected evaporated in vacuo

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

Procedure: 3-(2-Piperidinyl)-1-propanol (8.69 g, 60.7 mmol) was stirred in acetonitrile (90 ml) with triethylamine (10.40 mL, 74.6 mmol) under N2 and cooled in an ice bath. Benzyl chloroformate (9.53 ml, 66.7 mmol) was added dropwise. After complete addition the reaction was allowed to warm to ambient temperature and stirring then continued overnight. The suspension was filtered and the filtrate evaporated to dryness. The residue was partitioned between ethyl acetate and water. The organic phase was washed with saturated brine, passed through a hydrophobic frit and evaporated to dryness. The residue was purified by chromatography on silica (330 g silica RediSep column, loaded in DCM) using a 0-50% ethyl acetate in cyclohexane gradient over 40 mins. with a 50-100% flush of ethyl acetate on an ISCO Companion. No peaks were detected (254 nm, 280 nm) so the waste was evaporated in vacuo to recover the material. The material was re-columned using identical conditions as before but detecting at 220 nm and collecting all the eluent. The main product peak was collected and evaporated in vacuo to give the title compound as a yellow oil (6.15 g). LCMS (System B): tRET=2.46 min; MH+ 278 cooled in an ice bath After complete addition the reaction The suspension was filtered the filtrate evaporated to dryness The residue was partitioned between ethyl acetate and water The organic phase was washed with saturated brine evaporated to dryness The residue was purified by chromatography on silica (330 g silica RediSep column, loaded in DCM) over 40 mins with a 50-100% flush of ethyl acetate on an ISCO Companion was evaporated in vacuo to recover the material collecting all the eluent The main product peak was collected evaporated in vacuo