Yield:913191-20-5 91%

Reaction Conditions:

with ammonium hydroxide;iodine in tetrahydrofuran;water at 20; for 16 h;

Steps:

5.2 Step 2:
5-bromo-2-hydroxy-3-methylbenzonitrile

Iodine (5.08 g, 20 mmol) was added to a mixture of 5-bromo-2-hydroxy-3-methylbenzaldehyde (2.15 g, 10.0 mmol) in tetrahydrofuran (20 mL) and ammonium hydroxide (20 mL), and the reaction solution was stirred at room temperature for 16 h.
The reaction was quenched with a sodium bisulfite solution (50 mL), and then ethyl acetate (100 mL*2) was added for extraction.
The organic phases were combined, washed with saturated brine (100 mL*2), dried over anhydrous sodium sulfate, filtered, and concentrated to give 5-bromo-2-hydroxy-3-methylbenzonitrile in the form of a yellow solid (1.92 g, 91%), which was directly used in the next step without purification. LCMS (ESI) [M+H]⁺=211.9; tH NMR (400 MHz, CDCl₃) δ 7.50-7.42 (m, 2H), 5.99 (s, 1H), 2.27 (s, 3H).

References:

US2020/369676,2020,A1 Location in patent:Paragraph 0842; 0844