Yield:2011-48-5 80%

Reaction Conditions:

Stage #1: p-methoxybenzyl chloridewith hydrazine hydrate in methanol at 0 - 20; for 2 h;
Stage #2: with hydrogenchloride in 1,4-dioxane; for 3 h;

Steps:

D Step-D:
Synthesis of (4-methoxybenzyl)hydrazine hydrochloride (Intermediate C)

To a stirred solution of hydrazinehydrate (3.19 mL, 63.8 mmol) in methanol (5 mL) was added 1-(chloromethyl)-4-methoxybenzene (1 g, 6.38 mmol) at 0°C, and the mixture was stirred at room temperature for 2 hours.
The progress of the reaction was monitored by TLC.
After the reaction completed, the reaction mixture was distilled off under reduced pressure and extracted with ether.
The combined organic extracts were washed with water and brine, dried over anhydrous sodium sulfate, and distilled off under reduced pressure.
The crude compound was taken in dioxane (5 mL), 4.0M dioxane hydrochloric acid (2 mL) was added thereto, and the mixture was stirred at room temperature for 3 hours.
The precipitated solid was filtered, washed with ether and dried to obtain Compound C (1 g, 80%).
The same batch was repeated with the scales of 1 g, 50 g, 100 g and 350 g.
¹H NMR (400 MHz, DMSO-d₆): δ 7.68 (brs, 2H), 7.38 (dd, 2H), 6.85 (dd, 2H), 3.98 (s, 2H), 3.78 (s, 3H).

References:

EP3640253,2020,A1 Location in patent:Paragraph 0094-0095