1-oxaspiro[2.4]heptane

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

Procedure: Reaction between 1-oxaspiro[2.4]heptane and aniline 12 gives 3-hydroxy-3-(3-((1-hydroxycyclopentyl)methylamino)phenyl)propanenitrile.

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

Procedure: Reaction between 1-oxaspiro[2.4]heptane and 2-(3-(3-aminophenyl)propyl)isoindoline-1,3-dione gives 2-(3-(3-(((1-hydroxycyclopentyl)methyl)amino)phenyl)propyl)isoindoline-1,3-dione.

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of tert-butyl 4-{[(4-hydroxy-1,2-benzisoxazol-3-yl)oxy]methyl}piperidine-1-carboxylate (100 mg, 0.287 mmol, EXAMPLE 17, step 2), 1-oxaspiro[2.4]heptane (59.7 mg, 0.609 mmol), and potassium carbonate (156 mg, 1.13 mmol) in ethanol (2 mL) was heated at 80° C. for 5 h. After cooling to room temperature, the mixture was diluted with ethyl acetate (3 mL) and 5% aq. sodium chloride was added to the mixture. Organic layer was separated, washed with brine, dried over magnesium sulfate and concentrated in vacuo to give a solid. The residual solid was purified by NH gel column chromatography (ethyl acetate/hexane 1:2) to give 95 mg (74%) of the title compound as a white solid. After cooling to room temperature was added to the mixture Organic layer was separated washed with brine dried over magnesium sulfate concentrated in vacuo to give a solid The residual solid was purified by NH gel column chromatography (ethyl acetate/hexane 1:2)

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of tert-butyl 4-{[(4-hydroxy-1,2-benzisoxazol-3-yl)oxy]methyl}piperidine-1-carboxylate (100 mg, 0.287 mmol, EXAMPLE 17, step 2), 1-oxaspiro[2.4]heptane (59.7 mg, 0.609 mmol), and potassium carbonate (156 mg, 1.13 mmol) in ethanol (2 mL) was heated at 80° C. for 5 h. After cooling to room temperature, the mixture was diluted with ethyl acetate (3 mL) and 5% aq. sodium chloride was added to the mixture. Organic layer was separated, washed with brine, dried over magnesium sulfate and concentrated in vacuo to give a solid. The residual solid was purified by NH gel column chromatography (ethyl acetate/hexane 1:2) to give 95 mg (74%) of the title compound as a white solid. After cooling to room temperature was added to the mixture Organic layer was separated washed with brine dried over magnesium sulfate concentrated in vacuo to give a solid The residual solid was purified by NH gel column chromatography (ethyl acetate/hexane 1:2)

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

Procedure: Reaction between 1-oxaspiro[2.4]heptane and aniline 12 gives 3-hydroxy-3-(3-((1-hydroxycyclopentyl)methylamino)phenyl)propanenitrile.

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

Procedure: Reaction between 1-oxaspiro[2.4]heptane and 2-(3-(3-aminophenyl)propyl)isoindoline-1,3-dione gives 2-(3-(3-(((1-hydroxycyclopentyl)methyl)amino)phenyl)propyl)isoindoline-1,3-dione.

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

Procedure: Reaction between 1-oxaspiro[2.4]heptane and aniline 12 gives 3-hydroxy-3-(3-((1-hydroxycyclopentyl)methylamino)phenyl)propanenitrile.

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

Procedure: Reaction between 1-oxaspiro[2.4]heptane and 2-(3-(3-aminophenyl)propyl)isoindoline-1,3-dione gives 2-(3-(3-(((1-hydroxycyclopentyl)methyl)amino)phenyl)propyl)isoindoline-1,3-dione.