Paclitaxel → HCID 121380559, compound

HRID 2200849Notes

Reaction equation

HRID 2200849 reaction equation
CCN(C(C)C)C(C)C.Cl[C:11]([O:13][CH2:14][Cl:15])=[O:12].[CH3:16][C:17]1[C@@H:34]([O:35][C:36]([C@H:38]([OH:55])[C@@H:39]([NH:46][C:47]([C:49]2[CH:50]=[CH:51][CH:52]=[CH:53][CH:54]=2)=[O:48])[C:40]2[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=2)=[O:37])[CH2:33][C@:29]2([OH:56])[C:30]([CH3:32])([CH3:31])[C:18]=1[C@@H:19]([O:74][C:75]([CH3:77])=[O:76])[C:20]([C@@:22]1([CH3:73])[C@H:27]([C@@H:28]2[O:57][C:58]([C:60]2[CH:61]=[CH:62][CH:63]=[CH:64][CH:65]=2)=[O:59])[C@:26]2([O:68][C:69]([CH3:71])=[O:70])[CH2:66][O:67][C@@H:25]2[CH2:24][C@@H:23]1[OH:72])=[O:21]>ClCCl>[C:75]([O:74][C@@H:19]1[C:18]2[C:30]([CH3:31])([CH3:32])[C@@:29]([OH:56])([CH2:33][C@H:34]([O:35][C:36](=[O:37])[C@H:38]([O:55][C:11]([O:13][CH2:14][Cl:15])=[O:12])[C@@H:39]([NH:46][C:47](=[O:48])[C:49]3[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=3)[C:40]3[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=3)[C:17]=2[CH3:16])[C@@H:28]([O:57][C:58](=[O:59])[C:60]2[CH:65]=[CH:64][CH:63]=[CH:62][CH:61]=2)[C@@H:27]2[C@:26]3([O:68][C:69](=[O:70])[CH3:71])[CH2:66][O:67][C@@H:25]3[CH2:24][C@H:23]([OH:72])[C@@:22]2([CH3:73])[C:20]1=[O:21])(=[O:76])[CH3:77]

Participants

5

Reactant 3

HCID 36314PaclitaxelHCID 62754Chloromethyl chloroformateHCID 81531Diisopropylethylamine

Product 1

HCID 121380559HCID 121380559, compoundYield 70%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

DIPEA (0.026 g, 46.0 mmol, 4.0 eq) was added to a solution of chloromethyl chloroformate (CMCF) [8] (0.04 g, 23.0 mmol, 4.0 eq) in dry dichloromethane under an argon atmosphere at 0° C. To the above reaction mixture at 0° C., a solution of paclitaxel 14114 (0.10 g, 11.7 mmol, 1.0 eq) in dry dichloromethane (y ml) was added. The reaction mixture was stirred at room temperature for 16 h. reaction progress was monitored by TLC. After 16 h the reaction mixture was diluted with dichloromethane (25 ml), washed with a 10% solution of NaHCO3 (15 ml), brine (10 ml), and then dried over anhydrous Na2SO4. Evaporation of the solvents under vacuum gave a white solid, (2aR,4S,4aS,6R,9S,11S,12S,12aR,12bS)-9-(((2R,3S)-3-benzamido-2-(((chloromethoxy)carbonyl)oxy)-3-phenylpropanoyl)oxy)-12-(benzoyloxy)-4,11-dihydroxy-4a,8,13,13-tetramethyl-5-oxo-2a,3,4,4a,5,6,9,10,11,12,12a,12b-dodecahydro-1H-7,11-methanocyclodeca[3,4]benzo[1,2-b]oxete-6,12b-diyl diacetate [315], (0.08 g, 70%)

Workup

  1. customreaction progress
  2. washwashed with a 10% solution of NaHCO3 (15 ml), brine (10 ml)
  3. dry with materialdried over anhydrous Na2SO4
  4. customEvaporation of the solvents under vacuum

Sources & evidence

ORD record
ord-7ab5b3b563cd438c9772f06f58250876
Source dataset
uspto-grants-2016_06
Patent number
US09359376B2

Reaction notes

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