1-fluoro-3-(2-methylpropoxy)benzene

Conditions: temp:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 1-fluoro-3-isobutoxybenzene (1.7 g, 10 mmol, EXAMPLE 16, Step 1) in tetrahydrofuran (15 mL) was added dropwise s-BuLi (0.99 M in cyclohexane, 12 mL, 12 mmol) at −78° C. under nitrogen atmosphere, and the mixture was stirred for 1 h. N,N-dimethylformamide (1.2 mL, 15 mmol) was added to the mixture, and the mixture was warm to −20° C. After being stirred at −20° C. for 1 h, the mixture was quenched with aq. sodium hydrogencarbonate (30 mL). The mixture was extracted with ethyl acetate (60 mL) and washed with water (30 mL). The extract was dried over magnesium sulfate and concentrated in vacuo to give an oil. The residual oil was purified by silica gel column chromatography (hexane/ethyl acetate 30:1) to give 1.2 g (61%) of the title compound as a colorless oil. After being stirred at −20° C. for 1 h the mixture was quenched with aq. sodium hydrogencarbonate (30 mL) The mixture was extracted with ethyl acetate (60 mL) washed with water (30 mL) The extract was dried over magnesium sulfate concentrated in vacuo to give an oil The residual oil was purified by silica gel column chromatography (hexane/ethyl acetate 30:1)

Conditions: temp:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 1-fluoro-3-isobutoxybenzene (1.7 g, 10 mmol, EXAMPLE 16, Step 1) in tetrahydrofuran (15 mL) was added dropwise s-BuLi (0.99 M in cyclohexane, 12 mL, 12 mmol) at −78° C. under nitrogen atmosphere, and the mixture was stirred for 1 h. N,N-dimethylformamide (1.2 mL, 15 mmol) was added to the mixture, and the mixture was warm to −20° C. After being stirred at −20° C. for 1 h, the mixture was quenched with aq. sodium hydrogencarbonate (30 mL). The mixture was extracted with ethyl acetate (60 mL) and washed with water (30 mL). The extract was dried over magnesium sulfate and concentrated in vacuo to give an oil. The residual oil was purified by silica gel column chromatography (hexane/ethyl acetate 30:1) to give 1.2 g (61%) of the title compound as a colorless oil. After being stirred at −20° C. for 1 h the mixture was quenched with aq. sodium hydrogencarbonate (30 mL) The mixture was extracted with ethyl acetate (60 mL) washed with water (30 mL) The extract was dried over magnesium sulfate concentrated in vacuo to give an oil The residual oil was purified by silica gel column chromatography (hexane/ethyl acetate 30:1)

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

Procedure: The title compound was prepared according to the procedure described in Step 7 of EXAMPLE 7 using 3-fluorophenol and isobutyl bromide instead of methyl 4-[(4-{2-[(4-hydroxy-1,2-benzisoxazol-3-yl)oxy]ethyl}piperidin-1-yl)methyl]tetrahydro-2H-pyran-4-carboxylate and 2,2,2-trifluoroethyl trifluoromethanesulfonate.

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

Procedure: The title compound was prepared according to the procedure described in Step 7 of EXAMPLE 7 using 3-fluorophenol and isobutyl bromide instead of methyl 4-[(4-{2-[(4-hydroxy-1,2-benzisoxazol-3-yl)oxy]ethyl}piperidin-1-yl)methyl]tetrahydro-2H-pyran-4-carboxylate and 2,2,2-trifluoroethyl trifluoromethanesulfonate.