Benzoyl chloride → Paclitaxel

HRID 1885051Notes

Reaction equation

HRID 1885051 reaction equation
[CH3:1][C:2]1[C@@H:19]([O:20][C:21]([C@H:23]([OH:32])[C@@H:24]([NH2:31])[C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)=[O:22])[CH2:18][C@:14]2([OH:33])[C:15]([CH3:17])([CH3:16])[C:3]=1[C@@H:4]([O:51][C:52]([CH3:54])=[O:53])[C:5]([C@@:7]1([CH3:50])[C@H:12]([C@@H:13]2[O:34][C:35]([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)=[O:36])[C@:11]2([O:45][C:46]([CH3:48])=[O:47])[CH2:43][O:44][C@@H:10]2[CH2:9][C@@H:8]1[OH:49])=[O:6].C([O-])(O)=O.[Na+].[C:60](Cl)(=[O:67])[C:61]1[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=1.CCCCC>CCOC(C)=O.C(Cl)(Cl)Cl.CO>[CH3:1][C:2]1[C@@H:19]([O:20][C:21]([C@H:23]([OH:32])[C@@H:24]([NH:31][C:60]([C:61]2[CH:62]=[CH:63][CH:64]=[CH:65][CH:66]=2)=[O:67])[C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=2)=[O:22])[CH2:18][C@:14]2([OH:33])[C:15]([CH3:16])([CH3:17])[C:3]=1[C@@H:4]([O:51][C:52]([CH3:54])=[O:53])[C:5]([C@@:7]1([CH3:50])[C@H:12]([C@@H:13]2[O:34][C:35]([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)=[O:36])[C@:11]2([O:45][C:46]([CH3:48])=[O:47])[CH2:43][O:44][C@@H:10]2[CH2:9][C@@H:8]1[OH:49])=[O:6]

Participants

7

Reactant 4

HCID 7412Benzoyl chlorideHCID 8003PentaneHCID 516892Sodium BicarbonateHCID 9810701133524-70-6

Product 1

HCID 36314Paclitaxel

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolvent2×HCID 21584188Chloroform methanolSolvent

Procedure

In a 10 ml round-bottom flask, 0.031 g (0.041 mmol, 1.0 eq) of N-debenzoyl-paclitaxel were dissolved in 1.25 ml of AcOEt. The clear yellow solution was added with 1.25 ml of a NaHCO3 aqueous saturated solution. 7.1 ml (0.064 mmol, 1.5 eq) of benzoyl chloride were dropped into the resulting diphasic mixture, under strong magnetic stirring. The progress of the reaction was checked by TLC (SiO2, CHCl3/CH3OH 9:1). After disappearance of the starting product, a single spot having Rf=0.50 was observed. The reaction mixture was diluted with AcOEt. The organic phase was separated from the aqueous one, which was extracted with AcOEt (three extractions). The combined organic phases were dried over MgSO4, filtered and concentrated. The crude (0.037 g) was dissolved in a 1:1 mixture of CH2Cl2/ethyl ether, then n-pentane (0.030 g, 0.035 mmol, 86%) was added to precipitate paclitaxel, having the spectroscopic characteristics reported in literature.

Workup

  1. customThe organic phase was separated from the aqueous one, which
  2. extractionwas extracted with AcOEt (three extractions)
  3. dry with materialThe combined organic phases were dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. dissolutionThe crude (0.037 g) was dissolved in a 1:1 mixture of CH2Cl2/ethyl ether
  7. customto precipitate paclitaxel

Sources & evidence

ORD record
ord-2caf990f3aac4be593f7f8c8608f447e
Source dataset
uspto-grants-2004_07
Patent number
US06768012B2

Reaction notes

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