tert-Butyl 4-(4-fluoro-2-nitrophenyl)piperazine-1-carboxylate synthesis

Yield: 64%

Reaction Conditions:

with triethylamine at 50; for 16 h;

Steps:

2.1 Example 2.1: f-Butyl 4-(4-fluoro-2-nitrophenyl)piperazine-l-carboxylate
To a solution of 2,5-difluoronitrobenzene (3.2 mL; 29.5 mmol; Sigma-Aldrich) in ethanol (59 mL), was added l-Boc-piperazine (6.05 g; 32.5 mmol; Sigma-Aldrich) and triethylamine (4.11 mL; 29.5 mmol; Sigma-Aldrich), and the reaction mixture was stirred 16 h at 50°C and then allowed to cool to room temperature. The reaction mixture was evaporated and then extracted with ethyl acetate (30 mL). The extract was dried over anhydrous sodium sulfate, filtered, and evaporated to dryness, and the crude product was purified by silica chromatography (ethyl acetate/hexanes gradient). Yield: 6.18 g; 64%. 1H NMR (500 MHz, CDCh): d 7.51 (dd, 1H), 7.26-7.23 (m, 1H), 7.17 (dd, 1H), 3.56 (t, 4H), 2.95 (brs, 4H), 1.47 (s, 9H).

References:

RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY;EBRIGHT, Richard H.;EBRIGHT, Yon W.;LIN, Chih-Tsung WO2019/226915, 2019, A1 Location in patent:Page/Page column 50-51