Trifluoroacetic acid → Trifluoroacetate

반응식

[CH3:1][CH2:2][C@@:3]1([OH:59])[CH2:21][N:19]2[CH2:20][C@H:5]([CH2:6][C@:7]([C:55]([O:57][CH3:58])=[O:56])([C:22]3[CH:23]=[C:24]4[C@:32]56[C@@H:36]7[C@:37]([CH2:52][CH3:53])([C@@H:41]([O:48][C:49]([CH3:51])=[O:50])[C@:42]([OH:47])([C:43]([O:45][CH3:46])=[O:44])[C@@H:31]5[N:30]([CH3:54])[C:25]4=[CH:26][C:27]=3[O:28][CH3:29])[CH:38]=[CH:39][CH2:40][N:35]7[CH2:34][CH2:33]6)[C:8]3[NH:16][C:15]4[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=4[C:9]=3[CH2:17][CH2:18]2)[CH2:4]1.OS(O)(=O)=O.[Br:65]N1C(=O)CCC1=O.[F:73][C:74]([F:79])([F:78])[C:75]([OH:77])=[O:76]>>[CH3:1][CH2:2][C@@:3]1([OH:59])[CH2:21][N:19]2[CH2:20][C@@H:5]([CH2:6][C@:7]([C:55]([O:57][CH3:58])=[O:56])([C:22]3[CH:23]=[C:24]4[C@:32]56[C@@H:36]7[C@:37]([CH2:52][CH3:53])([C@@H:41]([O:48][C:49]([CH3:51])=[O:50])[C@:42]([OH:47])([C:43]([O:45][CH3:46])=[O:44])[C@@H:31]5[N:30]([CH3:54])[C:25]4=[CH:26][C:27]=3[O:28][CH3:29])[CH:38]=[CH:39][CH2:40][N:35]7[CH2:34][CH2:33]6)[C:8]3[NH:16][C:15]4[C:14]([Br:65])=[CH:13][CH:12]=[CH:11][C:10]=4[C:9]=3[CH2:17][CH2:18]2)[CH2:4]1.[F:73][C:74]([F:79])([F:78])[C:75]([O-:77])=[O:76]

참가 물질

반응물 3

HCID 6422Trifluoroacetic acid2회

HCID 67184N-bromobutanimide

HCID 5388983Vinblastine Sulfate

생성물 2

HCID 84468Trifluoroacetate수율 69%

HCID 7145379912'-Bromovinblastine

실험 절차

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]+.