Diisopropylethylamine → (2S,4R)-2-(3-Bromo-4-methoxycarbonyl-phenylcarbamoyl)-4-fluoro-pyrrolidine-1-carboxylic acid tert-butyl ester

Participants

Reaction Steps

A mixture of (2S,4R)-4-fluoro-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester (355 mg, 1.52 mmol), and 4-amino-2-bromo-benzoic acid methyl ester (prepared as described in Part C) (350 mg, 1.52 mmol), HBTU (865 mg, 2.282 mmol) and DIPEA (0.531 mL, 3.04 mmol) in CH2Cl2 (15 mL) was stirred at RT for 60 h. Additional aliquots of (2S,4R)-4-fluoro-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester (180 mg), HBTU (580 mg) and DIPEA (0.265 mL) were added to the mixture, and stirring was continued at RT for 20 h and subsequently at 40° C. for 24 h. The reaction mixture was diluted with CH2Cl2 and the organic layer was washed with water, 1N aqueous HCl (3×), aqueous NaHCO3 solution (2×) and brine, dried (Phase separator) and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (eluent: EtOAc/c-hexane gradient 1:3 to 1:2) to afford the title compound as a white foam. TLC Rf (EtOAc/c-hexane 1:2)=0.24; MS (LC/MS): 468 [M+Na]+, 388/390 [MH−tBu]+, 345/347 [MH−Boc]+; tR (HPLC conditions b): 4.36 min.

Provenance & Evidence