Dimethylformamide → 2-Bromo-6-chlorobenzaldehyde

Temperature

0 °C

A 1.6 molar solution of butyllithium in hexanes (4.5 mL, 2.8 mmol) was placed in a three-neck flask equipped with a stirrer, addition funnel, low-temperature thermometer and nitrogen inlet tube at 0° C. A solution of diisopropyl amine (1.13 mL, 8.1 mmol) in anhydrous tetrahydrofuran was added dropwise. The resulting solution was stirred at 0° C. for ten minutes, then cooled to −78° C. Upon cooling, a solution of 1-bromo-3-chlorobenzene (1.4 g, 7.3 mmol) in anhydrous tetrahydrofuran was added dropwise. The reaction was allowed to stir at −78° C. for one hour. Anhydrous dimethylformamide (636 μL) was added. The solution was allowed to slowly warm to room temperature, followed by the addition of acetic acid (50 mL) and water (50 mL). The aqueous mixture was extracted with ether twice and the ether layers were separated. The combined ether layers were successively washed with aqueous hydrochloric acid and brine. The separated organic layer was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by flash column chromatography on silica gel, eluting with 9:1 hexanes:ethyl acetate to yield 2-chloro-6-bromobenzaldehyde as an off white solid (850 mg, 53% yield). NMR (300 MHz, CDCl3): 10.4 (s, 1H), 7.6 (m, 1H), 7.45 (m, 1H), 7.3 ppm (m, 1H).

1. customequipped with a stirrer, addition funnel
2. customat 0° C
3. temperaturecooled to −78° C
4. temperatureUpon cooling
5. stirringto stir at −78° C. for one hour
6. temperatureto slowly warm to room temperature
7. extractionThe aqueous mixture was extracted with ether twice
8. customthe ether layers were separated
9. washThe combined ether layers were successively washed with aqueous hydrochloric acid and brine
10. dry with materialThe separated organic layer was dried over anhydrous sodium sulfate
11. filtrationfiltered
12. concentrationconcentrated under reduced pressure
13. customThe resulting residue was purified by flash column chromatography on silica gel
14. washeluting with 9:1 hexanes

ORD record

ord-ab9c2456fb4444ff91782e880549ea7a

Source dataset

uspto-grants-2006_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07115642B2