2-Fluoro-6-iodobenzaldehyde

Chemical Properties

off-white crystalline

Synthesis

Procedure: 1. To a solution of 1-fluoro-3-iodobenzene (5.00 g, 22.5 mmol) in tetrahydrofuran (THF, 50 mL) was slowly added lithium diisopropylammonium (LDA, 17.0 mL, 33.7 mmol) dropwise at -78 °C. The reaction temperature was maintained at -78 °C for 2 hours. After maintaining the reaction temperature at -78 °C and stirring for 2 h, N,N-dimethylformamide (DMF, 4.90 g, 67.5 mmol) was added and stirring was continued at -78 °C for 30 min. 2. Upon completion of the reaction, the reaction was quenched with an aqueous ammonium chloride solution (20 mL) and water (30 mL), followed by extraction with ethyl ether (3 x 30 mL). The organic layers were combined, washed sequentially with 2N hydrochloric acid (20 mL) and saturated saline (20 mL), and dried over anhydrous sodium sulfate.3. The solvent was removed by pressure-relief concentration, and the resulting crude product was purified by column chromatography on silica gel, with the eluent being petroleum ether/ethyl acetate (100:1 to 50:1), to give 6-fluoro-2-iodobenzaldehyde (3.7 g, 66% yield). The product was characterized by 1H NMR (DMSO-d6, 500 MHz): δ10.01 (s, 1H), 7.89-7.79 (m, 1H), 7.44-7.40 (m, 2H).

References

[1] Patent: WO2013/41539, 2013, A1. Location in patent: Page/Page column 55; 56
[2] Patent: US2014/206702, 2014, A1. Location in patent: Paragraph 0277
[3] Chemistry - A European Journal, 2013, vol. 19, # 27, p. 8875 - 8883
[4] Tetrahedron Letters, 1992, vol. 33, # 49, p. 7499 - 7502
[5] Bioorganic and Medicinal Chemistry Letters, 2005, vol. 15, # 12, p. 2998 - 3001