Diisopropylethylamine → 1,1-Dimethylethyl (2S)-2-[[[2-(4-bromophenyl)-2-oxoethyl]amino]carbonyl]-4,4-difluoro-1-pyrrolidinecarboxylate

Participants

Reaction Conditions

Reaction Steps

In a 50 mL pear-shaped flask, (S)-1-(tert-butoxycarbonyl)-4,4-difluoropyrrolidine-2-carboxylic acid (1 g, 3.98 mmol, Eq: 1.00) and HATU (1.51 g, 3.98 mmol, Eq: 1.00) were combined with DMF (15 ml) to give a colorless solution and stirred at 23° C. for 10 min. 2-Amino-1-(4-bromophenyl)ethanone HCl (995 mg, 3.98 mmol) was added followed by drop wise addition of DIPEA (1.54 g, 2.09 ml, 11.9 mmol). The suspension became a orange solution once the addition of the amine was completed. It was stirred at room temperature for 1 hr and diluted with brine (100 ml) and H2O (50 ml). The precipitate was filtered, washed with H2O and dried to afford (S)-tert-butyl2-(2-(4-bromophenyl)-2-oxoethylcarbamoyl)-4,4-difluoropyrrolidine-1-carboxylate as a light yellow solid. (1.8 g, >96%): ESI-LRMS m/e calcd for C18H21BrF2N2O4 [M+] 447. found 448 [M+H+].

Provenance & Evidence