2-Bromo-6-fluorobenzaldehyde

Uses

It is a important raw material and intermediate used in organic synthesis agrochemical, pharmaceutical and dyestuff field.

Synthesis

To a stirred solution of iPr2NH (2.25 mL, 1.63 g, 16.1 mmol) in THF (20 mL) containing a 50 mL three-necked flask under the protection of dry argon gas was added dropwise nBuLi (6.3 mL, 2.35 M in hexane, 14.7 mmol). The reaction mixture was stirred at 0°C for 10 min. Subsequently, after continued stirring at 0°C for 20 min, the mixture was cooled to -78°C and a solution of 1-bromo-3-fluorobenzene (2.45 g, 14.0 mmol) in THF (10 mL) was added dropwise over a 12-minute period, maintaining the temperature in the range of -85 to -75°C, to give a deep red solution. After stirring at -78°C for 1 h, a THF (7 mL) solution of DMF (1.32 g, 18.2 mmol) was added dropwise over 5 min and stirring was continued for 1 h at -78°C. The reaction mixture was quenched with AcOH (2.5 mL) and slowly warmed to room temperature. The reaction mixture was poured into a mixture of 0.2 M HCl (40 mL) and MeOAc (50 mL) and the organic layer was separated. The aqueous layer was extracted with MeOAc (30 mL), and the combined organic phases were washed with brine (60 mL), dried over Na2SO4, filtered and concentrated under reduced pressure to give an orange colored oil. The oil was purified by recrystallization from hexane to afford the target product 2-bromo-6-fluorobenzaldehyde SI-1f (2.31 g, 11.4 mmol, 81% yield).

References

[1] Journal of Organic Chemistry, 2013, vol. 78, # 15, p. 7741 - 7748
[2] Tetrahedron Letters, 2016, vol. 57, # 1, p. 11 - 14
[3] Patent: US2017/158680, 2017, A1. Location in patent: Paragraph 0361; 0362; 0363
[4] Patent: WO2014/169167, 2014, A1. Location in patent: Page/Page column 57; 58
[5] Bioorganic and Medicinal Chemistry Letters, 2005, vol. 15, # 12, p. 2998 - 3001