Trifluoroacetic acid → Trifluoroacetate

HRID 339717

反応式

HRID 339717 の反応式
[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]

参加物

5

反応物 3

HCID 6422Trifluoroacetic acid2 回HCID 67184N-bromobutanimideHCID 5388983Vinblastine Sulfate

生成物 2

HCID 84468Trifluoroacetate収率 69%HCID 7145379912'-Bromovinblastine

実験手順

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]+.

後処理

  1. concentrationthe reaction mixture was concentrated under reduced pressure
  2. additiondiluted with dichloromethane
  3. additionpoured into ice water
  4. washThe aqueous layer was washed 3× with dichloromethane
  5. customThe organic layer was separated
  6. extractionthe aqueous layer was extracted with dichloromethane (3×)
  7. washthe combined organic layers were washed with water
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated under reduced pressure
  10. customPurification by column chromatography (silica (deactivated by eluting with 10% triethylamine in hexane), EtOAc)
  11. customgave
  12. customPurification by reversed phase chromatography (C18, acetonitrile/water, 0.05% trifluoroacetic acid)

出典と根拠

ORDレコード
ord-c79afc1ad39b4321950345d6765f3af1
出典データセット
uspto-grants-2014_11
特許番号
US08895543B2

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