Paclitaxel → 1-[(1R,2S)-2-(Benzoylamino)-1-[[[(2aR,4S,4aS,6R,9S,11S,12S,12aR,12bS)-6,12b-bis(acetyloxy)-12-(benzoyloxy)-2a,3,4,4a,5,6,9,10,11,12,12a,12b-dodecahydro-4,11-dihydroxy-4a,8,13,13-tetramethyl-5-oxo-7,11-methano-1H-cyclodeca[3,4]benz[1,2-b]oxet-9-yl]oxy]carbonyl]-2-phenylethyl] pentanedioate

HRID 2414778Notes

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].ClC(Cl)(Cl)C[O:66][C:67](Cl)=[O:68]>N1C=CC=CC=1.ClCCl>[CH3:1][C:2]1[C@@H:19]([O:20][C:21]([C@H:23]([O:40][C:5]([CH2:4][CH2:3][CH2:2][C:67]([OH:66])=[O:68])=[O:6])[C@@H:24]([NH:31][C:32]([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=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]([CH3:16])([CH3:17])[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:50]=[CH:49][CH:48]=[CH:47][CH:46]=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]

Participants

Conditions

Temperature: -20 °C

Procedure

875 mg of paclitaxel was dissolved in 6 ml of pyridine and 40 ml of dichloromethane. The solution was cooled at −20° C. Three hundred microliters of trichloroethylchloroformate (Troc) (at −20° C.) was added by portions of 100 microliters and the solution was kept at −20°C. for two hours. An additional 100 microliters of Troc was added and the solution was stirred at room temperature for 20 hours. The solvent was evaporated to dryness. The residue was dissolved in 10 ml of dimethylformamide with 1.36 g of glutaric anhydride and 40 mg of dimethylaminopyridine. The solution was stirred at 85° C. for 20 hours. The product was precipitated with 10 volumes of water. The white precipitate was collected on a sintered glass filter and dried. The dried product was then dissolved in 20 ml of methanol:acetic acid (9:1) and 0.5 g of zinc powder was added. The solution was stirred at room temperature for 30 minutes. Zinc was filtered and the filtrate was evaporated to a volume of about 2 ml. 70 ml of dichloromethane was added and the solution was washed twice with 30 ml of 0.01N HCl, once with 30 ml of sodium bicarbonate and once with 50 ml of water. The organic phase was dried with anhydrous sodium sulfate, filtered and evaporated to dryness. This yielded 620 mg of a C7-glutaryl paclitaxel

Workup

customThe solvent was evaporated to dryness
dissolutionThe residue was dissolved in 10 ml of dimethylformamide with 1.36 g of glutaric anhydride and 40 mg of dimethylaminopyridine
stirringThe solution was stirred at 85° C. for 20 hours
customThe product was precipitated with 10 volumes of water
customThe white precipitate was collected on a sintered glass
filtrationfilter
customdried
dissolutionThe dried product was then dissolved in 20 ml of methanol:acetic acid (9:1)
addition0.5 g of zinc powder was added
stirringThe solution was stirred at room temperature for 30 minutes
filtrationZinc was filtered
customthe filtrate was evaporated to a volume of about 2 ml
addition70 ml of dichloromethane was added
washthe solution was washed twice with 30 ml of 0.01N HCl, once with 30 ml of sodium bicarbonate and once with 50 ml of water
dry with materialThe organic phase was dried with anhydrous sodium sulfate
filtrationfiltered
customevaporated to dryness

Sources & evidence

ORD record: ord-18e783f3927146cc98eb9a02d6caefa0
Source dataset: uspto-grants-2004_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06815462B2

Reaction notes

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