General procedure for the synthesis of tert-butyl 4-(2-fluoro-4-nitrophenyl)piperazine-1-carboxylate:
1. 1-(2-fluoro-4-nitrophenyl)piperazine (12.5 g, 55.8 mmol) was dissolved in 1,4-dioxane (108 mL) under cooling conditions in an ice bath.
2. 1N sodium hydroxide solution (54 mL) and di-tert-butyl dicarbonate (14 mL, 61.38 mmol) were added sequentially to the above solution.
3. The temperature of the reaction mixture was adjusted to 25-35°C and stirred continuously for 0.5 hours.
4. Upon completion of the reaction, the mixture was poured into ice-cold water (200 mL) and a yellow precipitate was precipitated.
5. The precipitate was collected by filtration through a Büchner funnel to afford the target product tert-butyl 4-(2-fluoro-4-nitrophenyl)piperazine-1-carboxylate (18.0 g, 99% yield).
Product characterization data:
1H NMR (CDCl3): δ 8.01-7.88 (m, 2H), 6.93 (t, J = 8.6 Hz, 1H), 3.61 (t, J = 4.9 Hz, 4H), 3.24 (t, J = 4.9 Hz, 4H), 1.49 (s, 9H).
IR (KBr, cm-1): 3119, 1692, 1605, 1512.
CI-MS (m/z): 326 (M++1), 270, 240, 226, 195, 183, 131, 96.
