Synthesis
Synthesis of Intermediate 46: 3-(Isoxazol-4-yl)benzaldehyde: Step 1: Synthesis of 4-iodoisoxazole: To a solution of N-iodosuccinimide (NIS, 23.0 g, 100 mmol) in trifluoroacetic acid (TFA, 200 mL) was added isoxazole (6.9 g, 100 mmol) all at once at room temperature. The reaction mixture was stirred for 18 hours. After completion of the reaction, the mixture was partitioned between petroleum ether (PE, 200 mL) and water (1000 mL). The organic phase was separated, washed with saturated sodium bisulfate solution, dried over anhydrous sodium sulfate (Na2SO4), filtered and concentrated to give the yellow solid product 4-iodoisoxazole (1.2 g, 7% yield).
References
[1] Angewandte Chemie - International Edition, 2016, vol. 55, # 43, p. 13580 - 13584
[2] Angew. Chem., 2016, vol. 128, p. 13778 - 13782,5
[3] Patent: US2006/46991, 2006, A1. Location in patent: Page/Page column 50
[4] Patent: WO2006/21886, 2006, A1. Location in patent: Page/Page column 83
[5] Patent: WO2011/38204, 2011, A1. Location in patent: Page/Page column 150
