2-fluoro-6-(2-methylpropoxy)benzaldehyde

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

Procedure: 50% aq. Sodium hydroxide (1.2 mL, 15.0 mmol) was added to a mixture of 2-fluoro-6-isobutoxybenzaldehyde (1.2 g, 6.1 mmol, EXAMPLE 16, Step 2) and hydroxylamine hydrochloride (0.47 g, 6.7 mmol) in ethanol (24 mL) and water (48 mL) at 0° C. The mixture was warmed to room temperature and stirred for 3 h. The mixture was neutrized with 2N hydrochloric acid and extracted with dichloromethane (100 mL×2). The combined extracts were dried over magnesium sulfate and concentrated in vacuo to give a solid. The residual solid was purified by silica gel column chromatography (hexane/ethyl acetate 9:1 to 6:1) to give 0.99 g (77%) of the title compound as a white solid. extracted with dichloromethane (100 mL×2) The combined extracts were dried over magnesium sulfate concentrated in vacuo to give a solid The residual solid was purified by silica gel column chromatography (hexane/ethyl acetate 9:1 to 6:1)

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

Procedure: 50% aq. Sodium hydroxide (1.2 mL, 15.0 mmol) was added to a mixture of 2-fluoro-6-isobutoxybenzaldehyde (1.2 g, 6.1 mmol, EXAMPLE 16, Step 2) and hydroxylamine hydrochloride (0.47 g, 6.7 mmol) in ethanol (24 mL) and water (48 mL) at 0° C. The mixture was warmed to room temperature and stirred for 3 h. The mixture was neutrized with 2N hydrochloric acid and extracted with dichloromethane (100 mL×2). The combined extracts were dried over magnesium sulfate and concentrated in vacuo to give a solid. The residual solid was purified by silica gel column chromatography (hexane/ethyl acetate 9:1 to 6:1) to give 0.99 g (77%) of the title compound as a white solid. extracted with dichloromethane (100 mL×2) The combined extracts were dried over magnesium sulfate concentrated in vacuo to give a solid The residual solid was purified by silica gel column chromatography (hexane/ethyl acetate 9:1 to 6:1)

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:-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)