2-chloro-3-(1,3-dioxolan-2-yl)-6-fluorobenzaldehyde

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: To a solution of ethyltriphenylphosphonium bromide (3.43 g) in tetrahydrofuran (15 mL) was added potassium tert-butoxide (1.31 g) at 0° C., and the mixture was stirred at room temperature for 1 hr. Successively, 2-chloro-3-(1,3-dioxolan-2-yl)-6-fluorobenzaldehyde (1.35 g) was added to the mixture, and the mixture was stirred for 2.5 hr. To the reaction mixture was added saturated brine, and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give crude 2-{2-chloro-4-fluoro-3-[prop-1-en-1-yl]phenyl}-1,3-dioxolane (1.41 g). the mixture was stirred for 2.5 hr the mixture was extracted with ethyl acetate The extract was dried over anhydrous magnesium sulfate concentrated under reduced pressure

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of diisopropylamine (4.25 mL) in tetrahydrofuran (25 ml) was added dropwise 1.6 mol/L solution (18.9 mL) of n-butyllithium in hexane at −78° C., and the mixture was stirred at 0° C. for 1 hr. To the prepared lithium diisopropylamide was added dropwise a solution of 2-(2-chloro-4-fluorophenyl)-1,3-dioxolane (5.34 g) in tetrahydrofuran (25 mL) at −78° C. The mixture was stirred at the same temperature for 1 hr, and N,N-dimethylformamide (2.3 mL) was added thereto. The reaction mixture was stirred for 30 min, and acetic acid was added thereto. After the temperature of the reaction mixture was raised to room temperature, water was added to the mixture, and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent: hexane-ethyl acetate=9:1→1:1) and recrystallized from hexane to give the title compound as a colorless solid (yield: 3.96 g). The mixture was stirred at the same temperature for 1 hr The reaction mixture was stirred for 30 min After the temperature of the reaction mixture was raised to room temperature the mixture was extracted with ethyl acetate The extract was dried over anhydrous magnesium sulfate concentrated under reduced pressure The obtained residue was purified by silica gel column chromatography (developing solvent: hexane-ethyl acetate=9:1→1:1) recrystallized from hexane