tert-butyl 4-(2-aminoethyl)-4-hydroxypiperidine-1-carboxylate

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Chloroacetyl chloride (0.483 mL) was added dropwise over 10 minutes to a vigorously stirred mixture at 0° C. of tert-butyl 4-(2-aminoethyl)-4-hydroxypiperidine-1-carboxylate (example 89, step b) (1.1 g) in ethyl acetate (25 mL) and potassium carbonate (1.77 g) dissolved in water (20 mL). The mixture was then stirred at 0° C. for 45 minutes before being extracted with ethyl acetate. The organic layer was dried over sodium sulphate, filtered and the solvent evaporated under reduced pressure. The crude product was purified by flash silica chromatography eluting with ethyl acetate. Pure fractions were evaporated to dryness to afford the subtitled compound. Yield 0.9 g. before being extracted with ethyl acetate The organic layer was dried over sodium sulphate filtered the solvent evaporated under reduced pressure The crude product was purified by flash silica chromatography eluting with ethyl acetate Pure fractions were evaporated to dryness

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

Procedure: A solution of tert-butyl 4-(cyanomethyl)-4-hydroxypiperidine-1-carboxylate (example 89, step a) (1.4 g) in a mixture of ethanol (20 mL) and acetic acid (20 mL) was hydrogenated at 4 atmospheres pressure of hydrogen in the presence of platinum(IV) oxide (0.25 g) for 4 hours. The catalyst was filtered off and the solvents removed under reduced pressure. The residue was partitioned between dilute aqueous NaOH and ethyl acetate and the organic layer dried over sodium sulphate, filtered and the solvent evaporated under reduced pressure to afford the subtitled compound. Yield 1.1 g. Used directly. The catalyst was filtered off the solvents removed under reduced pressure The residue was partitioned between dilute aqueous NaOH and ethyl acetate the organic layer dried over sodium sulphate filtered the solvent evaporated under reduced pressure

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

Procedure: A solution of tert-butyl 4-(cyanomethyl)-4-hydroxypiperidine-1-carboxylate (example 89, step a) (1.4 g) in a mixture of ethanol (20 mL) and acetic acid (20 mL) was hydrogenated at 4 atmospheres pressure of hydrogen in the presence of platinum(IV) oxide (0.25 g) for 4 hours. The catalyst was filtered off and the solvents removed under reduced pressure. The residue was partitioned between dilute aqueous NaOH and ethyl acetate and the organic layer dried over sodium sulphate, filtered and the solvent evaporated under reduced pressure to afford the subtitled compound. Yield 1.1 g. Used directly. The catalyst was filtered off the solvents removed under reduced pressure The residue was partitioned between dilute aqueous NaOH and ethyl acetate the organic layer dried over sodium sulphate filtered the solvent evaporated under reduced pressure

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Chloroacetyl chloride (0.483 mL) was added dropwise over 10 minutes to a vigorously stirred mixture at 0° C. of tert-butyl 4-(2-aminoethyl)-4-hydroxypiperidine-1-carboxylate (example 89, step b) (1.1 g) in ethyl acetate (25 mL) and potassium carbonate (1.77 g) dissolved in water (20 mL). The mixture was then stirred at 0° C. for 45 minutes before being extracted with ethyl acetate. The organic layer was dried over sodium sulphate, filtered and the solvent evaporated under reduced pressure. The crude product was purified by flash silica chromatography eluting with ethyl acetate. Pure fractions were evaporated to dryness to afford the subtitled compound. Yield 0.9 g. before being extracted with ethyl acetate The organic layer was dried over sodium sulphate filtered the solvent evaporated under reduced pressure The crude product was purified by flash silica chromatography eluting with ethyl acetate Pure fractions were evaporated to dryness

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

Procedure: A solution of tert-butyl 4-(cyanomethyl)-4-hydroxypiperidine-1-carboxylate (example 89, step a) (1.4 g) in a mixture of ethanol (20 mL) and acetic acid (20 mL) was hydrogenated at 4 atmospheres pressure of hydrogen in the presence of platinum(IV) oxide (0.25 g) for 4 hours. The catalyst was filtered off and the solvents removed under reduced pressure. The residue was partitioned between dilute aqueous NaOH and ethyl acetate and the organic layer dried over sodium sulphate, filtered and the solvent evaporated under reduced pressure to afford the subtitled compound. Yield 1.1 g. Used directly. The catalyst was filtered off the solvents removed under reduced pressure The residue was partitioned between dilute aqueous NaOH and ethyl acetate the organic layer dried over sodium sulphate filtered the solvent evaporated under reduced pressure

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Chloroacetyl chloride (0.483 mL) was added dropwise over 10 minutes to a vigorously stirred mixture at 0° C. of tert-butyl 4-(2-aminoethyl)-4-hydroxypiperidine-1-carboxylate (example 89, step b) (1.1 g) in ethyl acetate (25 mL) and potassium carbonate (1.77 g) dissolved in water (20 mL). The mixture was then stirred at 0° C. for 45 minutes before being extracted with ethyl acetate. The organic layer was dried over sodium sulphate, filtered and the solvent evaporated under reduced pressure. The crude product was purified by flash silica chromatography eluting with ethyl acetate. Pure fractions were evaporated to dryness to afford the subtitled compound. Yield 0.9 g. before being extracted with ethyl acetate The organic layer was dried over sodium sulphate filtered the solvent evaporated under reduced pressure The crude product was purified by flash silica chromatography eluting with ethyl acetate Pure fractions were evaporated to dryness

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

Procedure: A solution of tert-butyl 4-(cyanomethyl)-4-hydroxypiperidine-1-carboxylate (example 89, step a) (1.4 g) in a mixture of ethanol (20 mL) and acetic acid (20 mL) was hydrogenated at 4 atmospheres pressure of hydrogen in the presence of platinum(IV) oxide (0.25 g) for 4 hours. The catalyst was filtered off and the solvents removed under reduced pressure. The residue was partitioned between dilute aqueous NaOH and ethyl acetate and the organic layer dried over sodium sulphate, filtered and the solvent evaporated under reduced pressure to afford the subtitled compound. Yield 1.1 g. Used directly. The catalyst was filtered off the solvents removed under reduced pressure The residue was partitioned between dilute aqueous NaOH and ethyl acetate the organic layer dried over sodium sulphate filtered the solvent evaporated under reduced pressure