tert-butyl 4-(cyanomethyl)-4-hydroxypiperidine-1-carboxylate

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

Procedure: A solution of tert-butyl 1-oxa-6-azaspiro[2.5]octane-6-carboxylate (2 g) in DMF (20 mL) was treated with potassium cyanide (0.672 g) and the resultant mixture stirred at 20° C. for 4 days. The mixture was partitioned between ethyl acetate and brine, the organic layer was washed twice with brine, dried over sodium sulphate, filtered and the solvent evaporated under reduced pressure. The crude product was purified by flash silica chromatography using 60% ethyl acetate in isohexane as solvent. Pure fractions were evaporated to dryness to afford the subtitled compound. Yield 1.18 g. The mixture was partitioned between ethyl acetate and brine the organic layer was washed twice with brine dried over sodium sulphate filtered the solvent evaporated under reduced pressure The crude product was purified by flash silica chromatography 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 1-oxa-6-azaspiro[2.5]octane-6-carboxylate (2 g) in DMF (20 mL) was treated with potassium cyanide (0.672 g) and the resultant mixture stirred at 20° C. for 4 days. The mixture was partitioned between ethyl acetate and brine, the organic layer was washed twice with brine, dried over sodium sulphate, filtered and the solvent evaporated under reduced pressure. The crude product was purified by flash silica chromatography using 60% ethyl acetate in isohexane as solvent. Pure fractions were evaporated to dryness to afford the subtitled compound. Yield 1.18 g. The mixture was partitioned between ethyl acetate and brine the organic layer was washed twice with brine dried over sodium sulphate filtered the solvent evaporated under reduced pressure The crude product was purified by flash silica chromatography 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 1-oxa-6-azaspiro[2.5]octane-6-carboxylate (2 g) in DMF (20 mL) was treated with potassium cyanide (0.672 g) and the resultant mixture stirred at 20° C. for 4 days. The mixture was partitioned between ethyl acetate and brine, the organic layer was washed twice with brine, dried over sodium sulphate, filtered and the solvent evaporated under reduced pressure. The crude product was purified by flash silica chromatography using 60% ethyl acetate in isohexane as solvent. Pure fractions were evaporated to dryness to afford the subtitled compound. Yield 1.18 g. The mixture was partitioned between ethyl acetate and brine the organic layer was washed twice with brine dried over sodium sulphate filtered the solvent evaporated under reduced pressure The crude product was purified by flash silica chromatography Pure fractions were evaporated to dryness