Trifluoroacetic acid → Trifluoroacetate

A solution of vinblastine sulfate (0.5 g, 0.55 mmol) in trifluoroacetic acid (50 mL) under nitrogen was stirred at room temperature for 20 min. The flask was wrapped with foil to keep the reaction mixture in the dark and a solution of N-bromosuccinimide (103 mg, 0.58 mmol) in trifluoroacetic acid (25 mL) was added dropwise. After stirring for 18 h, the reaction mixture was concentrated under reduced pressure, diluted with dichloromethane, and poured into ice water. The aqueous layer was washed 3× with dichloromethane. The pH of the mixture was adjusted to 11-12 with 3% NH3 (aq). The organic layer was separated and the aqueous layer was extracted with dichloromethane (3×) and the combined organic layers were washed with water, dried (Na2SO4), and concentrated under reduced pressure. Purification by column chromatography (silica (deactivated by eluting with 10% triethylamine in hexane), EtOAc) gave a mixture of mono and dibromides (0.33 g, 65%). Purification by reversed phase chromatography (C18, acetonitrile/water, 0.05% trifluoroacetic acid) gave 12′-bromovinblastine as a trifluoroacetate (0.42 g, 69%). 1H NMR (300 MHz, CDCl3) δ 8.09 (s, 1H), 7.62 (d, J=2 Hz, 1H), 7.21 (dd, J=9, 2 Hz, 1H), 6.97 (d, J=9 Hz, 1H), 6.52 (s, 1H), 6.10 (s, 1H), 5.85 (dd, J=9, 4 Hz, 1H), 5.46 (s, 1H), 5.30 (d, J=9 Hz, 1H), 3.89 (m, 2H), 3.80 (s, 6H), 3.73 (s, 1H), 3.65 (m, 1H), 3.63 (s, 3H), 3.50-2.90 (m, 6H), 2.85 (m, 3H), 2.71 (s, 3H), 2.62 (s, 1H), 2.53-2.38 (m, 2H), 2.36-2.10 (m, 2H), 2.11 (s, 3H), 1.90-1.70 (m, 3H), 1.54-1.25 (m, 7H), 0.89 (t, J=7 Hz, 3H), 0.77 (t, J=7 Hz, 3H); ESI MS m/z 889, 891 [M+H]+.