Tetrahydrofuran → 1-Methylpyridin-1-ium 4-methylbenzenesulfonate

HRID 962920

반응식

HRID 962920 반응식
CC1[C@@H](OC([C@H](O)[C@@H:24]([NH:31][C:32]([C:34]2[CH:35]=[CH:36][CH:37]=CC=2)=O)C2C=CC=CC=2)=O)C[C@]2(O)C(C)(C)C=1[C@@H](OC(C)=O)C([C@@]1(C)[C@H]([C@@H]2OC(C2C=CC=CC=2)=O)[C@]2(OC(C)=O)CO[C@@H]2C[C@@H]1O)=O.C(N(CC)CC)C.[S:70]([C:74]1[CH:80]=[CH:79][C:77]([CH3:78])=[CH:76][CH:75]=1)([O-:73])(=[O:72])=[O:71].FC1C=CC=C[N+]=1C.O1CCCC1>OP(O)=O.O[Mo](O)(=O)=O.O>[S:70]([C:74]1[CH:80]=[CH:79][C:77]([CH3:78])=[CH:76][CH:75]=1)([O-:73])(=[O:72])=[O:71].[CH3:24][N+:31]1[CH:32]=[CH:34][CH:35]=[CH:36][CH:37]=1

참가 물질

7

반응물 4

HCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 36314Paclitaxel2회HCID 1716312-Fluoro-1-methylpyridinium p-toluenesulfonate

생성물 1

HCID 115218291-Methylpyridin-1-ium 4-methylbenzenesulfonate

시약·촉매·용매 2

HCID 21863154Dihydroxy(dioxo)molybdenum;phosphonic acid촉매HCID 962Water용매

실험 절차

Taxol-2'-MPT (methylpyridinium tosylate) was synthesized according to the method of T. Mukaiyama, Angewandte Chemie 1979, 18(18), 707-808. Taxol (10 mg, 0.012 mM), from NaPro Biochemicals, Boulder Colo., USA, was dried by azeotropic distillation with toluene (2×1.0 mL) and then dissolved in methylene chloride (0.4 mL) and treated sequentially under an atmosphere of dry argon, with freshly distilled triethylamine (5 microL, 0.04 mM, 3 equivalents) and 2-fluoro-1-methylpyridinium tosylate (5 mg, 0.018 mM, 1.5 equivalents) Aldrich Chemicals, and allowed to stir at ambient temperature for 30 minutes. The clear colorless solution rapidly turned to a clear pale yellow. The course of the reaction was monitored through thin layer chromatography (TLC) (E. Merck RP-18 silica, 65 tetrahydrofuran:35 water, UV/phosphomolybdic acid) and after thirty minutes of stirring at ambient temperature, judged complete as no taxol remained and only one compound was apparent by TLC (Rf 0.8). Purification via reverse phase high pressure liquid chromatography (HPLC) (C18 column, 1 mM NH4OAc pH 6.5 buffer/methanol gradient, 1.5 mL/min. UV) to give, after removal of solvent in vaccuo, pure taxol-2'-MPT (2) (12 mg, 93% yield) as a white amorphous solid. All spectroscopic data (1H NMR and HRMS) were in accord with the structure assigned to taxol-2'-MPT. 1H NMR (CDCl3, 125 MHz) δ: 1.055 (s, 3H, C17-H), 1.083 (s, 3H, C19-H), 1.724 (s, 3H, C19-H), 1.858 (m, 1H, C6-βH), 1.913 (s, 3H, CH3 -Ph), 2.193 (s, 3H, C10-OC(O)CH3), 2.514 (m, 1H, C6-aH), 3.663 (d, 1H, J=7.0 Hz, C3-H), 4.110 (d, 1H, J=8.5, C20-aH, A of AB), 4.133 (s, 3H, N--CH3), 4.230 (d, 1H, J=8.5, C20-aH, B of AB), 4.315 (dd, 1H, J=8.7, 10.7, C7-H), 4.901 (dd, 1H, J=1.0, 7.7, C5-H), 5.501 (d, 1H, C2-H, J=7.0), 5.702 (bt, 1H, C2'-H, J=8.0), 5.951 (dd, 1H, C13-H, J=1.0, 8.0), 6.120 (bd, 1H, C3'-H, J=10.0), 6.181 (s, 1H, C10-H) 7.702 (t, 1H, N--H, J=7.5), 7.33-7.45 (m, 8H, Ar--H), 7.56-7.62 (m, 4H, Ar--H), 7.56-7.62 (m, 4H, Ar--H), 7.68-7.75 (m, 4H, Ar--H), 8.00-8.05 (m, 1H Ar--H), 8.23-8.28 (m, 1H, Pyr-H), 8.41 (m, 1H, Pyr-H). IR (neat, KCl plate) cm-1 : 3640-3120 (bm), 3030-2870 (bm), 2320 (m), 1720 (s), 1630 (m), 1560 (m), 1500 (m), 1360 (s), 1160 (m), 1070 (m), 700 (m). UV/Vis (CHCl3) nm: 254, 280. FAB HRMS: calc for C53H57 O14N2 : 945.3810; found: 945.3810.

후처리

  1. dry with material, USA, was dried by azeotropic distillation with toluene (2×1.0 mL)
  2. dissolutiondissolved in methylene chloride (0.4 mL)
  3. stirringof stirring at ambient temperature
  4. customPurification via reverse phase high pressure liquid chromatography (HPLC) (C18 column, 1 mM NH4OAc pH 6.5 buffer/methanol gradient, 1.5 mL/min. UV)
  5. customto give

출처 및 근거

ORD 기록
ord-94f14f95c1c94c8282cf93fb6b9c0509
출처 데이터셋
uspto-grants-1998_06
특허 번호
US05760240

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