Hydrazine, [(2,4-difluorophenyl)methyl]- (9CI) synthesis

Yield:627076-28-2 96%

Reaction Conditions:

with hydrazine in methanol at 0 - 20;

Steps:

56.1

A 2-necked 250 mL round-bottomed flask was charged with hydrazine (40 mL, 41 g, 1.3 mol) and cooled to 0° C. with an ice water bath. A solution of 2,4-difluorobenzyl bromide (15.5 mL, 25.0 g, 121 mmol) in 20 mL anhydrous methanol was added from an addition funnel over 1 hour. The ice water bath was then removed, and the solution allowed to stir at room temperature overnight. The methanol was removed by evaporation, and the product extracted out of the hydrazine with ether (3×). The ethereal solution was evaporated to give a clear yellowish oil of sufficient purity to be used directly in the next step (18.2 g, 96% yield): ¹H NMR (DMSO-d₆) δ 7.41-7.53 (m, 1H), 7.15 (ddd, J=10.4, 9.5, 2.7 Hz, 1H), 7.00-7.07 (m, 1H), 3.74 (s, 2H), 3.45 (br. s., 3H).

References:

US2011/105509,2011,A1 Location in patent:Page/Page column 33; 34