(4-Fluoro-3-methoxy-phenyl)-hydrazine hydrochloride synthesis

Yield:327021-81-8 67%

Reaction Conditions:

Stage #1: 4-fluoro-3-methoxyanilinewith hydrogenchloride in water at 0 - 20; for 0.333333 h;
Stage #2: with sodium nitrite in water at -5 - 20; for 2 h;
Stage #3: with hydrogenchloride;tin(ll) chloride in water at -5 - 20; for 3 h;

Steps:

A.36a; A.37a; A.38a

To stirred hydrochloric acid (100 mL) at 0° C. was added 3-methoxy-4-fluoroaniline (10 g, 71 mmol) followed by water (10 mL) and more hydrochloric acid (10 mL). The mixture was warmed to room temperature, stirred for 20 min then cooled to -5° C. A solution of sodium nitrite (5.14 g, 75 mmol) in water (25 mL) was added dropwise such that the internal temperature remained below 0° C. The mixture was warmed to room temperature and stirred for 2 h. The mixture was cooled to -5° C. and a solution of tin(II)chloride dihydrate (64 g, 284 mmol) in hydrochloric acid (200 mL) was added dropwise such that the internal temperature remained below 0° C. The mixture was warmed to room temperature, stirred for 3 h then filtered. The filter cake was washed with hydrochloric acid and dried under vacuum to give a pink solid (7.4 g). The precipitate from the combined filtrates was filtered-off, washed (hydrochloric acid) and dried under vacuum to give a further crop of product (1.8 g. to give a combined yield of 9.2 g, 67%).

References:

US6706750,2004,B1 Location in patent:Page/Page column 15