(5-CHLORO-2-METHOXY-PHENYL)-HYDRAZINE HYDROCHLORIDE synthesis

Yield:5446-16-2 90%

Reaction Conditions:

Stage #1: 5-chloro-2-methoxyanilinewith hydrogenchloride;sodium nitrite in water at -5 - 0; for 1 h;
Stage #2: with hydrogenchloride;tin(ll) chloride in water at -5 - 20;Concentration;Time;

Steps:

A Intermediate 7A:

To a solution of 2-methoxy-5-chloroaniline (100 g, 0.636 mol) in 6 N HC1 (600 mL) was added slowly an aqueous solution of sodium nitrite (52.7 g, 0.764 mol) maintaining the temperature between -5 to 0 °C. The reaction mixture was then stirred for about 1 h maintaining the temperature below 0 °C. A solution of stannous chloride (362 g, 1.90 mol) in cone. HC1 was added slowly at -5 to 0 °C and stirring was continued for another 1.5 h after which the reaction mixture was brought to room temperature slowly. The white solid was then filtered, washed with 2 N HC1 to remove the stannous chloride, and then washed with diethyl ether and air-dried to give Intermediate 7A (120 g, yield: 90.0%). NMR (400 MHz, DMSO-d₆) δ 3.82 (s, 3H, OCH₃), 6.95 - 7.00 (m, 2 H), 7.135 - 7.139 (d, 1 H), 10.28 (bs, 3 H, NH and NH₂). ¹³C NMR (100 MHz, DMSO-d₆) δ 56.48, 112.61, 114.37, 121.59, 124.75, 135.95, 146.82.

References:

WO2014/22349,2014,A1 Location in patent:Paragraph 00167