Hydrochloric Acid → 4-Chloro-2-fluoro-3-methoxybenzaldehyde

Temperature

-49 °C

To a solution of 2-chloro-6-fluoroanisole (321.2 g) in 2 L of dry tetrahydrofuran (THF), cooled to −70° C., was added 890 mL of 2.5 M n-BuLi in hexane over 30 min with good mechanical stirring. During the addition the reaction warmed to −48 to −50° C. and was held there for 15 min after addition was complete. The solution was cooled to −75° C. before a solution of 177 g of dimethylformamide (DMF) in 100 mL of THF was added keeping the temperature below −50° C. The reaction was warmed to room temperature and 260 g of 37% aqueous HCl was slowly added and stirring was continued for 2 hours. The phases were separated and the organic phase concentrated and taken into 2 L of ether. The solution was washed twice with 500 mL of aqueous 10% HCl. The organic phase was dried over MgSO4, filtered and concentrated to 372 g of a light gold oil (93% pure by GC). This oil was distilled bulb to bulb to give 282 g (75% yield) of a light gold oil that solidified upon standing. A small sample was crystallized from pentane to give fine white needles; MP 44-45° C.; 1H NMR (CDCl3, 300 MHz) δ 10.3 (s, 1H); 7.5 (dd, 1H, J=6.6, 8.5 Hz); 7.3 (m, 1H); 4.0 (s, 3H).

1. additionDuring the addition the reaction
2. additionafter addition
3. additionwas added
4. customthe temperature below −50° C
5. temperatureThe reaction was warmed to room temperature
6. waitwas continued for 2 hours
7. customThe phases were separated
8. concentrationthe organic phase concentrated
9. washThe solution was washed twice with 500 mL of aqueous 10% HCl
10. dry with materialThe organic phase was dried over MgSO4
11. filtrationfiltered
12. concentrationconcentrated to 372 g of a light gold oil (93% pure by GC)
13. distillationThis oil was distilled bulb to bulb

ORD record

ord-6e4271858e7d42cfa2f6e9b2657c0378

Source dataset

uspto-grants-2009_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07611647B2