Dimethylformamide → 5-Chloro-2-methylbenzaldehyde

Temperature

-78 °C

Into a flame-dried 250 mL round-bottom flask equipped with a magnetic stir bar and under N2 was added 2-bromo-4-chlorotoluene (10.0 mL, 75.0 mmol) in anhydrous THF (150 mL). The clear sol. was cooled to −78° C. and BuLi (36.6 mL, 82.4 mmol, 2.25 M sol. in hexanes) was added dropwise over 20 min. The resulting light orange sol. was stirred at −78° C. for 1 h, and DMF (30 mL, 375 mmol) was added in a single addition. The resulting mixture was allowed to warm to rt over 4 h. The reaction was quenched by addition of aq. 1M HCl (20 mL), and stirred at rt overnight. The reaction mixture was poured into a 500 mL separatory funnel containing aq. 1M HCl (200 mL). The mixture was extracted with Et2O (3×100 mL). The combined org. layers were washed with brine, dried over MgSO4, filtered, and concentrated under reduced pressure to a yellow oil. Purification by short-path distillation under reduced pressure (≈1 mm Hg) yielded the title compound as a light yellow oil (7.99 g, 69%). bp=70-72° C. at 1 mm Hg.

1. customInto a flame-dried 250 mL round-bottom flask equipped with a magnetic stir bar and under N2
2. temperatureto warm to rt over 4 h
3. customThe reaction was quenched by addition of aq. 1M HCl (20 mL)
4. stirringstirred at rt overnight
5. additionThe reaction mixture was poured into a 500 mL separatory funnel
6. additioncontaining aq. 1M HCl (200 mL)
7. extractionThe mixture was extracted with Et2O (3×100 mL)
8. washlayers were washed with brine
9. dry with materialdried over MgSO4
10. filtrationfiltered
11. concentrationconcentrated under reduced pressure to a yellow oil
12. customPurification
13. distillationby short-path distillation under reduced pressure (≈1 mm Hg)

ORD record

ord-0ccdba2f0c4e4b289ca99f79275fd381

Source dataset

uspto-grants-2011_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07968720B2