(4-Chloro-2-methoxy-phenyl)-hydrazine hydrochloride synthesis

Yield:1567373-49-2 93%

Reaction Conditions:

Stage #1: 4-chloro-o-anisidinewith hydrogenchloride;acetic acid;sodium nitrite in water at 0 - 60; for 1.5 h;
Stage #2: with hydrogenchloride;tin(ll) chloride in water at 0; for 0.5 h;

Steps:

7.B

General procedure: B. To a suspension of compound 7b (1 .69 g, 10.7 mmol, 1 eq) in concentrated HCl (25 mL) and acetic acid (10 mL) at 0 °C was added a solution of sodium nitrite (740 mg, 10.7 mmol, 1 eq) in water (10 mL) dropwise. The suspension was warmed to 60 °C for 1.5 hrs. The solution was cooled to 0 °C and a solution of SnCl₂ (5.32 g, 23.6 mmol, 2.2 eq) in concentrated HCl (25 mL) was added. After 30 minutes, a precipatate was collected by filtration to give compound 7c (2.06 g, 93%). 1H NMR (DMSO-d6) δ: 9.94 (br. s., 2H), 7.72 (br. s., 1H), 7.07 (s, 1H), 7.00 (s, 2H). 3.85 (s, 3H). Following the procedure described above for Example 7 and substituting the appropriate reagents, starting materials and purification methods known to those skilled in the art, the following intermediates to compounds of the present invention were prepared:

References:

WO2014/28805,2014,A1 Location in patent:Page/Page column 65; 66