1-(2-Fluoro-4-nitrophenyl)piperazine synthesis

Yield: 37%

Reaction Conditions:

Stage #1:4-(2-fluoro-4-nitrophenyl)-piperazine-1-carboxylic acid tert butyl ester with hydrogenchloride in ethyl acetate at 0 - 20; for 12 h;
Stage #2: with sodium hydrogencarbonate in water;ethyl acetate; pH=9

Steps:

52 Preparation of 1-(2-fluoro-4-nitrophenyl)piperazine
Reference Example 52 Preparation of 1-(2-fluoro-4-nitrophenyl)piperazine 4N Hydrogen chloride/ethyl acetate solution (10.0 ml, 40.0 mmol) was added to a solution of 4-(2-fluoro-4-nitrophenyl)piperazine-1-carboxylic acid tert-butyl ester (compound of Reference Example 14; 2.50 g, 7.68 mmol) in ethyl acetate (10 ml) under ice cooling, and the mixture was stirred at room temperature for 12 hours. The reaction mixture was adjusted to pH=9 by addition of saturated aqueous sodium hydrogencarbonate, and concentrated under reduced pressure. The obtained solid was collected by filtration and washed with water to give the title compound (0.563 g, 37%) as a yellow solid. ¹H-NMR (CD₃OD) δ: 2.98-3.05 (4H, m), 3.26-3.33 (4H, m), 7.12 (1H, t, J=9.0 Hz), 7.94 (1H, dd, J=13.5, 3.0 Hz), 8.02 (1H, ddd, J=9.0, 2.7, 0.9 Hz).

References:

INSTITUTE OF MEDICINAL MOLECULAR DESIGN. INC. US2008/227784, 2008, A1 Location in patent:Page/Page column 39