Paclitaxel → HCID 121380549, compound

HRID 2200847Notes

Reaction equation

HRID 2200847 reaction equation
[CH3:1][C:2]1[C@@H:19]([O:20][C:21]([C@H:23]([OH:40])[C@@H:24]([NH:31][C:32]([C:34]2[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=2)=[O:33])[C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=2)=[O:22])[CH2:18][C@:14]2([OH:41])[C:15]([CH3:17])([CH3:16])[C:3]=1[C@@H:4]([O:59][C:60]([CH3:62])=[O:61])[C:5]([C@@:7]1([CH3:58])[C@H:12]([C@@H:13]2[O:42][C:43]([C:45]2[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=2)=[O:44])[C@:11]2([O:53][C:54]([CH3:56])=[O:55])[CH2:51][O:52][C@@H:10]2[CH2:9][C@@H:8]1[OH:57])=[O:6].Cl.[C:64](Cl)(=[O:71])[C:65]1[CH:70]=[CH:69][CH:68]=[N:67][CH:66]=1>N1C=CC=CC=1.ClCCl>[C:60]([O:59][C@@H:4]1[C:3]2[C:15]([CH3:16])([CH3:17])[C@@:14]([OH:41])([CH2:18][C@H:19]([O:20][C:21](=[O:22])[C@H:23]([O:40][C:64](=[O:71])[C:65]3[CH:70]=[CH:69][CH:68]=[N:67][CH:66]=3)[C@@H:24]([NH:31][C:32](=[O:33])[C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)[C:25]3[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=3)[C:2]=2[CH3:1])[C@@H:13]([O:42][C:43](=[O:44])[C:45]2[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=2)[C@@H:12]2[C@:11]3([O:53][C:54](=[O:55])[CH3:56])[CH2:51][O:52][C@@H:10]3[CH2:9][C@H:8]([OH:57])[C@@:7]2([CH3:58])[C:5]1=[O:6])(=[O:61])[CH3:62]

Participants

5

Reactant 2

HCID 36314PaclitaxelHCID 884383-Pyridinecarbonyl chloride, hydrochloride (1:1)

Product 1

HCID 121380549HCID 121380549, compoundYield 45%

Reagents, catalysts & solvents 2

HCID 1049PyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

4 drops of pyridine were added to a solution of paclitaxel [4114] (0.10 g, 0.117 mmol 1.0 eq) of in dry dichloromethane under argon atmosphere. At 0° C., nicotinoyl chloride hydrochloride [296] (0.17 g, 1.17 mmol 10.0 eq) was added. The reaction mixture was stirred at room temperature for 24 hours. After 24 hours, the mixture was diluted with dichloromethane (25 ml) and washed with a 10% solution of NaHCO3 (15 ml) and brine (10 ml) followed by drying over anhydrous sodium sulfate. Evaporation of the solvents provided residual yellow solid which was purified by silica gel column chromatography (30% ethyl acetate: cyclohexane, 100-200 mesh silica) to get a white solid [310], (2aR,4S,4aS,6R,9S,11S,12S,12aR,12bS)-9-(((2R,3S)-3-benzamido-2-(nicotinoyloxy)-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, (0.05 g, 45%)

Workup

  1. waitAfter 24 hours
  2. washwashed with a 10% solution of NaHCO3 (15 ml) and brine (10 ml)
  3. dry with materialby drying over anhydrous sodium sulfate
  4. customEvaporation of the solvents
  5. customprovided residual yellow solid which
  6. customwas purified by silica gel column chromatography (30% ethyl acetate: cyclohexane, 100-200 mesh silica)

Sources & evidence

ORD record
ord-8cd99550bb2f4654b6bff977fee0fe18
Source dataset
uspto-grants-2016_06
Patent number
US09359376B2

Reaction notes

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