Diisopropylamine → 2-Chloro-4-fluoro-3-formylbenzonitrile

Temperature

0 °C

To a solution (300 mL) of diisopropylamine (12.4 mL) in tetrahydrofuran was added dropwise 1.6 mol/L solution (55.4 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 (70 mL) of 2-chloro-4-fluorobenzonitrile (12.0 g) in tetrahydrofuran at −78° C. After the reaction mixture was stirred at the same temperature for 1 hr, N,N-dimethylformamide (6.90 mL) was added thereto. The reaction mixture was stirred for 30 min, and acetic acid (20 mL) was added thereto. The temperature of the mixture was raised to room temperature, saturated brine was added to the mixture and the mixture was extracted with ethyl acetate. The extract was dried over magnesium sulfate and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent: hexane-ethyl acetate=30:1→1:1) and recrystallized from a mixed solvent of isopropyl ether and hexane to give the title compound as a yellow solid (yield: 5.94 g).

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

ORD record

ord-ee2fe085a2fb4d9dbdb15d564a0aca17

Source dataset

uspto-grants-2013_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08592452B2