Diisopropylamine → 2-Chloro-3-(1,3-dioxolan-2-yl)-6-fluorobenzaldehyde

Temperature

0 °C

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).

1. stirringThe mixture was stirred at the same temperature for 1 hr
2. stirringThe reaction mixture was stirred for 30 min
3. temperatureAfter the temperature of the reaction mixture was raised to room temperature
4. extractionthe mixture was extracted with ethyl acetate
5. dry with materialThe extract was dried over anhydrous magnesium sulfate
6. concentrationconcentrated under reduced pressure
7. customThe obtained residue was purified by silica gel column chromatography (developing solvent: hexane-ethyl acetate=9:1→1:1)
8. customrecrystallized from hexane

ORD record

ord-4912fc9c92da464594441bc657d97d18

Source dataset

uspto-grants-2013_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08592452B2