1-tert-butyl 2-methyl (2S)-4-methylidenepyrrolidine-1,2-dicarboxylate → 5-Azaspiro[2.4]heptane-5,6-dicarboxylic acid, 1,1-dibroMo-, 5-(1,1-diMethylethyl) 6-Methyl ester, (6S)-

Participants

Reaction Conditions

Reaction Steps

To a mixture of (S)-1-tert-butyl 2-methyl 4-methylenepyrrolidine-1,2-dicarboxylate (6 g, 24.9 mmol) and tetrabutylammonium bromide (161 mg, 0.02 eq) in anhydrous 1,2-dichloroethane (60 mL, 10 volumes) was added sodium tribromoacetate (17.48 g, 2.2 eq). The mixture was degassed and filled with N2 gas. It was heated at 70° C. for 2.5 hrs before additional sodium tribromoacetate (2.4 g, 0.3 eq) was added. The mixture was heated at 70° C. for 40 min. After the completion of the reaction, it was allowed to cool to room temperature and evaporated. The residue was diluted with 30% hexanes in tert-butyl methyl ether (100 mL) and filtered through a pad of celite. The filtrate was washed with water and brine, dried (Na2SO4), filtered and evaporated to dryness. The residue was passed through a silica gel (5.5 wt. volumes) pad with 0-15% tert-butyl methyl ether in hexanes and concentrated to afford the title compound (9.09 g, 88%) as a yellow oil as a mixture of two regioisomers. 1H NMR (500 MHz, CDCl3): 4.63-4.44 (m, 1H), 3.92-3.86 (m, 1H), 3.79 and 3.74 (2 s, 3H), 3.53-3.42 (m, 1H), 2.83-2.35 (m, 1.5H), 1.91-1.70 (m, 2.5H), 1.48 and 1.43 (2 s, 9H). ESI MS m/z (M+H)+ 413.85.

Provenance & Evidence