2-(6-bromo-3-ethoxy-2-fluorophenyl)-1,3-dioxolane

Conditions: temp:-70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under a nitrogen atmosphere, n-BuLi (43.3 mL, 71.42 mmol) was slowly added dropwise, at −70° C. or lower, to a THF (200 mL) solution of compound (54) (19.8 g, 68.02 mmol). The reaction mixture was agitated at −70° C. or lower for 1 hour, and then trimethyl borate (10.6 g, 102.0 mmol) was slowly added dropwise thereto. The reaction mixture was returned to room temperature, and then quenched with 200 mL of 2N hydrochloric acid aqueous solution, and extracted with 100 mL of toluene three times. Combined organic layers were washed with a saturated aqueous solution of sodium hydrogencarbonate, water and saturated brine, and then dried over magnesium sulfate, and a solvent was distilled off by an evaporator. The residue was washed with heptane, and thus (4-ethoxy-3-fluoro-2-formylphenyl)boronic acid (55) (9.85 g, yield 68.3%) was obtained. was returned to room temperature quenched with 200 mL of 2N hydrochloric acid aqueous solution extracted with 100 mL of toluene three times Combined organic layers were washed with a saturated aqueous solution of sodium hydrogencarbonate, water and saturated brine dried over magnesium sulfate a solvent was distilled off by an evaporator The residue was washed with heptane

Conditions: temp:-70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under a nitrogen atmosphere, n-BuLi (43.3 mL, 71.42 mmol) was slowly added dropwise, at −70° C. or lower, to a THF (200 mL) solution of compound (54) (19.8 g, 68.02 mmol). The reaction mixture was agitated at −70° C. or lower for 1 hour, and then trimethyl borate (10.6 g, 102.0 mmol) was slowly added dropwise thereto. The reaction mixture was returned to room temperature, and then quenched with 200 mL of 2N hydrochloric acid aqueous solution, and extracted with 100 mL of toluene three times. Combined organic layers were washed with a saturated aqueous solution of sodium hydrogencarbonate, water and saturated brine, and then dried over magnesium sulfate, and a solvent was distilled off by an evaporator. The residue was washed with heptane, and thus (4-ethoxy-3-fluoro-2-formylphenyl)boronic acid (55) (9.85 g, yield 68.3%) was obtained. was returned to room temperature quenched with 200 mL of 2N hydrochloric acid aqueous solution extracted with 100 mL of toluene three times Combined organic layers were washed with a saturated aqueous solution of sodium hydrogencarbonate, water and saturated brine dried over magnesium sulfate a solvent was distilled off by an evaporator The residue was washed with heptane

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

Procedure: A Dean-Stark condenser was attached, and a mixture of compound (53) (17.0 g, 68.81 mmol), EG (12.8 g, 200.2 mmol) and PTSA (0.17 g, 1 wt %) was refluxed in a toluene (200 mL) solvent for 3 hours. The reaction mixture was washed with a saturated aqueous solution of sodium hydrogencarbonate, water and saturated brine, and dried over magnesium sulfate. Toluene was distilled off by evaporator, and thus 2-(6-bromo-3-ethoxy-2-fluorophenyl)-1,3-dioxolane (54) (19.8 g, yield 98.8%) was obtained. The reaction mixture was washed with a saturated aqueous solution of sodium hydrogencarbonate, water and saturated brine dried over magnesium sulfate Toluene was distilled off by evaporator

Conditions: temp:-70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under a nitrogen atmosphere, n-BuLi (43.3 mL, 71.42 mmol) was slowly added dropwise, at −70° C. or lower, to a THF (200 mL) solution of compound (54) (19.8 g, 68.02 mmol). The reaction mixture was agitated at −70° C. or lower for 1 hour, and then trimethyl borate (10.6 g, 102.0 mmol) was slowly added dropwise thereto. The reaction mixture was returned to room temperature, and then quenched with 200 mL of 2N hydrochloric acid aqueous solution, and extracted with 100 mL of toluene three times. Combined organic layers were washed with a saturated aqueous solution of sodium hydrogencarbonate, water and saturated brine, and then dried over magnesium sulfate, and a solvent was distilled off by an evaporator. The residue was washed with heptane, and thus (4-ethoxy-3-fluoro-2-formylphenyl)boronic acid (55) (9.85 g, yield 68.3%) was obtained. was returned to room temperature quenched with 200 mL of 2N hydrochloric acid aqueous solution extracted with 100 mL of toluene three times Combined organic layers were washed with a saturated aqueous solution of sodium hydrogencarbonate, water and saturated brine dried over magnesium sulfate a solvent was distilled off by an evaporator The residue was washed with heptane

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

Procedure: A Dean-Stark condenser was attached, and a mixture of compound (53) (17.0 g, 68.81 mmol), EG (12.8 g, 200.2 mmol) and PTSA (0.17 g, 1 wt %) was refluxed in a toluene (200 mL) solvent for 3 hours. The reaction mixture was washed with a saturated aqueous solution of sodium hydrogencarbonate, water and saturated brine, and dried over magnesium sulfate. Toluene was distilled off by evaporator, and thus 2-(6-bromo-3-ethoxy-2-fluorophenyl)-1,3-dioxolane (54) (19.8 g, yield 98.8%) was obtained. The reaction mixture was washed with a saturated aqueous solution of sodium hydrogencarbonate, water and saturated brine dried over magnesium sulfate Toluene was distilled off by evaporator