1007881-98-2

15761-39-4

7644-04-4

1007881-98-2

General procedure for the synthesis of tert-butyl (S)-2-((2-(4-bromophenyl)-2-oxoethyl)carbamoyl)pyrrolidine-1-carboxylate from BOC-L-proline and 2-amino-4'-bromoacetophenone: in dry DMF (600 mL), 2-amino-1-(4-bromophenyl)acetophenone (50 g, 0.2 mol), BOC-L -proline (43.0 g, 0.2 mol), HATU (53 g, 0.21 mol) and N,N-diisopropylethylamine (80.0 g, 0.62 mol). The reaction mixture was stirred at 5 °C for 1 hour. After completion of the reaction, most of the DMF was removed by distillation under reduced pressure, and the residue was dissolved in ethyl acetate (600 mL) and washed sequentially with saturated aqueous NaHCO3 solution (500 mL) and brine (500 mL). The organic layer was dried over anhydrous MgSO4, filtered and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography with the eluent of petroleum ether/ethyl acetate (3:1 to 1:1) to afford the light yellow solid intermediate I-11 (60 g, 62% yield).1H NMR (400 MHz, CDCl3) δ: 7.85 (d, J = 8.4 Hz, 2H), 7.66 (d, J = 8.4 Hz, 2H), 4.67-4.80 ( m, 2H), 4.33-4.41 (m, 1H), 3.42-3.53 (m, 2H), 2.19-2.31 (m, 2H), 1.90-2.00 (m, 2H), 1.50 (s, 9H), 1.10.