反应详情

To a solution of (2R,3R)-3-fluoro-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester (45.0 mg, 0.193 mmol) in CH2Cl2 (5 mL) were added successively 3-chloro-2-fluorobenzylamine (0.024 mL, 0.193 mmol), HBTU (110 mg, 0.289 mmol) and DIPEA (0.067 mL, 0.386 mmol), and stirring was continued at RT for 20 h. The reaction mixture was then diluted with CH2Cl2, and the organics were washed with 0.1N aqueous HCl (2×), aqueous NaHCO3 (2×) and brine (1×), dried (Phase separator) and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (eluent: EtOAc/c-hexane gradient 1:4 to 1:3) to afford the title compound. TLC Rf (EtOAc/c-hexane 1:1)=0.31; MS (LC/MS): 397 [M+Na]+, 319 [MH−tBu]+, 275 [MH−Boc]+; tR (HPLC conditions b): 4.37 min.

1. washthe organics were washed with 0.1N aqueous HCl (2×), aqueous NaHCO3 (2×) and brine (1×)
2. customdried (Phase separator)
3. concentrationconcentrated in vacuo
4. customThe residue was purified by flash column chromatography on silica gel (eluent: EtOAc/c-hexane gradient 1:4 to 1:3)