183133-94-0

Basic information

• Product Name: (2aR,4S,4aS,6R,9S,11S,12S,12aR,12bS)-12b-(Acetyloxy)-12-(benzoyloxy)-1,2a,3,4,4a,6,9,10,11,12,12a,12b-dodecahydro-9,11-dihydroxy-4,6-dimethoxy-4a,8,13,13-tetramethyl-7,11-methano-5H-cyclodeca[3,4]benz[1,2-b]oxet-5-one
• Synonyms: 7β,10β-diMethoxy-10-deacetylbaccatin III;Cabazitaxel interMediate 1;7,10-MeO-10-DAB;7β,10β-Dimethoxy-10-dabⅢ;7β,10β-diMethoxy-10-DAB-II;(2aR,4S,4aS,6R,9S,11S,12S,12aR,12bS)-12b-(Acetyloxy)-12-(benzoyloxy)-1,2a,3,4,4a,6,9,10,11,12,12a,12b-dodecahydro-9,11-dihydroxy-4,6-diMethoxy-4a,8,13,13-tetraMethyl-7,11-Methano-5H-cyclodeca[3,4]benz[1,2-b]oxe;7,1-DiMethoxy-1-DAB III;2α,3ξ,5β,7β,10β,13α)-4-Acetoxy-1,13-dihydroxy-7,10-diMethoxy-9-oxo-5,20-epoxytax-11-en-2-yl benzoate
• CAS NO: 183133-94-0
• Molecular Formula: C₃₁H₄₀O₁₀
• Molecular Weight: 572.6433
• EINECS: 1592732-453-0
• Product Categories: API
• Mol File: 183133-94-0.mol
• Article Data: 20

Chemical Properties

• Boiling Point: 675.8±55.0 °C(Predicted)
• Appearance: /
• Density: 1.31
• Storage Temp.: Sealed in dry,Room Temperature
• Solubility: DMF (Slightly, Heated, Sonicated), DMSO (Very Slightly, Heated), Methanol and Wa
• PKA: 12.82±0.70(Predicted)
• Stability: Hygroscopic
• CAS DataBase Reference: (2aR,4S,4aS,6R,9S,11S,12S,12aR,12bS)-12b-(Acetyloxy)-12-(benzoyloxy)-1,2a,3,4,4a,6,9,10,11,12,12a,12b-dodecahydro-9,11-dihydroxy-4,6-dimethoxy-4a,8,13,13-tetramethyl-7,11-methano-5H-cyclodeca[3,4]benz[1,2-b]oxet-5-one(CAS DataBase Reference)
• NIST Chemistry Reference: (2aR,4S,4aS,6R,9S,11S,12S,12aR,12bS)-12b-(Acetyloxy)-12-(benzoyloxy)-1,2a,3,4,4a,6,9,10,11,12,12a,12b-dodecahydro-9,11-dihydroxy-4,6-dimethoxy-4a,8,13,13-tetramethyl-7,11-methano-5H-cyclodeca[3,4]benz[1,2-b]oxet-5-one(183133-94-0)
• EPA Substance Registry System: (2aR,4S,4aS,6R,9S,11S,12S,12aR,12bS)-12b-(Acetyloxy)-12-(benzoyloxy)-1,2a,3,4,4a,6,9,10,11,12,12a,12b-dodecahydro-9,11-dihydroxy-4,6-dimethoxy-4a,8,13,13-tetramethyl-7,11-methano-5H-cyclodeca[3,4]benz[1,2-b]oxet-5-one(183133-94-0)

Safety Data

• Hazardous Substances Data: 183133-94-0(Hazardous Substances Data)

Usage

Description

Cabazitaxel is a kind of Second line Drug for the treatment of prostate cancer, FDA Priority Review status approval listing is obtained because its curative effect is remarkable, for the advanced prostate cancer patients to the invalid even aggravation of Docetaxel, the first-selected medicine being used for the treatment of late period, hormone antagonist type prostate cancer.7,10-dimethoxy-10-Dab III is the important intermediate preparing Cabazitaxel.

Uses

4-Deacetyl-4-propionyl Cabazitaxel is an impurity of Cabazitaxel (C046500).A novel semi-synthetic taxane with antitumor activity used for the treatment of castration-resistant prostate cancer. A microtubule inhibitor.

Synthesis

Solvent is methylene dichloride, and alkali is the two dimethylamino naphthalene of 1,8-, and the mol ratio of 10-deacetylate Bakating III and trimethylammonium oxygen Tetrafluoroboric acid is 1:35; The mol ratio of 10-deacetylate Bakating III and alkali is 1:45;By 10-Dab (10g, 18.4mmol) be dissolved in methylene dichloride (200ml), add 1, the two dimethylamino naphthalene (177.2g of 8-, 828mmol), stirring at room temperature half an hour, add trimethylammonium oxygen Tetrafluoroboric acid (95.2g, 643.4mmol) again, stirring at room temperature 20h, suction filtration reaction solution, filter cake methylene dichloride washes 3 times, collects filtrate, and after concentrated, column chromatography (chloroform: methyl alcohol=100:3) obtains 7,10-dimethoxy-10Dab III 4.6g, yield 43.7%.

InChI:InChI=1S/C31H40O10/c1-16-19(33)14-31(36)26(40-27(35)18-11-9-8-10-12-18)24-29(5,25(34)23(38-7)22(16)28(31,3)4)20(37-6)13-21-30(24,15-39-21)41-17(2)32/h8-12,19-21,23-24,26,33,36H,13-15H2,1-7H3/t19-,20-,21+,23+,24?,26-,29+,30-,31+/m0/s1

Synthetic route

10-deacetylbaccatin III (32981-86-5) + carbonic acid dimethyl ester (616-38-6) → 4α-acetoxy-2α-benzoyloxy-5β,20-epoxy-1β,13α-dihydroxy-7β,10β-dimethoxy-9-oxo-11-taxene (183133-94-0)

Conditions	Yield
With dmap; caesium bromide; sodium hydride In tetrahydrofuran; N,N-dimethyl-formamide at -30℃; for 3h; Temperature; Reagent/catalyst;	89.6%

10-deacetylbaccatin III (32981-86-5) + methyl trifluoromethanesulfonate (333-27-7) → 4α-acetoxy-2α-benzoyloxy-5β,20-epoxy-1β,13α-dihydroxy-7β,10β-dimethoxy-9-oxo-11-taxene (183133-94-0)

Conditions	Yield
Stage #1: 10-deacetylbaccatin III With lithium hexamethyldisilazane In tetrahydrofuran at -72℃; for 0.666667h; Inert atmosphere; Stage #2: methyl trifluoromethanesulfonate In tetrahydrofuran at -72℃; for 4.08333h; Inert atmosphere;	87%
Stage #1: 10-deacetylbaccatin III With n-butyllithium In tetrahydrofuran at -78 - -35℃; for 1h; Inert atmosphere; Stage #2: methyl trifluoromethanesulfonate In tetrahydrofuran for 1h; Temperature;	55%

7,10-methylthiomethyl-10-deacetylbaccatin III (709673-79-0) → 4α-acetoxy-2α-benzoyloxy-5β,20-epoxy-1β,13α-dihydroxy-7β,10β-dimethoxy-9-oxo-11-taxene (183133-94-0)

Conditions	Yield
With water; Raney nickel In methanol at 23℃;	61%

4α-acetoxy-2α-benzoyloxy-5β,20-epoxy-10β-methoxy-9-oxo-1β,13α,7β-trihydroxy-11-taxene (183133-97-3) + methyl iodide (74-88-4) → 4α-acetoxy-2α-benzoyloxy-5β,20-epoxy-1β,13α-dihydroxy-7β,10β-dimethoxy-9-oxo-11-taxene (183133-94-0)

Conditions	Yield
With potassium hydride In tetrahydrofuran at 0 - 20℃;	61%
With sodium hydride In N,N-dimethyl acetamide at -15 - -5℃; for 1h; Concentration;	58.8%
With sodium hydride In N,N-dimethyl acetamide at -15 - -10℃; Time;	58.8%
Stage #1: 4α-acetoxy-2α-benzoyloxy-5β,20-epoxy-10β-methoxy-9-oxo-1β,13α,7β-trihydroxy-11-taxene; methyl iodide In N,N-dimethyl-formamide at 20 - 30℃; for 0.5h; Stage #2: With sodium hydride In N,N-dimethyl-formamide; paraffin oil at 0 - 5℃; Reagent/catalyst; Solvent; Temperature;

13-acetyl-7,10-dimethoxy-10-DAB (1402820-67-0) → 4α-acetoxy-2α-benzoyloxy-5β,20-epoxy-1β,13α-dihydroxy-7β,10β-dimethoxy-9-oxo-11-taxene (183133-94-0)

Conditions	Yield
With hydrazine hydrate In N,N-dimethyl-formamide at 23℃; for 18h; Inert atmosphere;	53%

10-deacetylbaccatin III (32981-86-5) + methyl iodide (74-88-4) → 4α-acetoxy-2α-benzoyloxy-5β,20-epoxy-1β,13α-dihydroxy-7β,10β-dimethoxy-9-oxo-11-taxene (183133-94-0)

Conditions	Yield
Stage #1: 10-deacetylbaccatin III With n-butyllithium In tetrahydrofuran at -75 - -35℃; for 1h; Inert atmosphere; Stage #2: methyl iodide for 1h;	52%
With potassium hydride In tetrahydrofuran at -20 - 20℃; for 8h;
With sodium hydride In tetrahydrofuran; mineral oil at 0 - 25℃; for 7.5h; Reagent/catalyst; Temperature; Solvent; Time;
With caesium bromide; sodium hydride In tetrahydrofuran; N,N-dimethyl-formamide at -20 - 20℃; for 2.33333h; Inert atmosphere;
With sodium hydride In N,N-dimethyl-formamide for 1.5h; Solvent; Temperature;	10 g

4α-acetoxy-2α-benzoyloxy-5β,20-epoxy-1β,10β-dihydroxy-9-oxo-7β,13α-di(triethylsilyloxy)-11-taxene (183133-99-5) → 4α-acetoxy-2α-benzoyloxy-5β,20-epoxy-1β,13α-dihydroxy-7β,10β-dimethoxy-9-oxo-11-taxene (183133-94-0)

Conditions	Yield
Multi-step reaction with 4 steps 1: sodium hydride / tetrahydrofuran / -5 - 0 °C 2: tetrabutyl ammonium fluoride / tetrahydrofuran / 0 - 5 °C / Inert atmosphere 3: sodium hydride / tetrahydrofuran / -5 - 0 °C 4: tetrabutyl ammonium fluoride / tetrahydrofuran / 0 - 5 °C / Inert atmosphere View Scheme
Multi-step reaction with 4 steps 1: sodium hydride / tetrahydrofuran / -5 - 0 °C 2: tetrabutyl ammonium fluoride / tetrahydrofuran / 0 - 5 °C / Inert atmosphere 3: sodium hydride / -5 - 0 °C 4: tetrabutyl ammonium fluoride / tetrahydrofuran / 0 - 5 °C / Inert atmosphere View Scheme
Multi-step reaction with 3 steps 1: triethylamine tris(hydrogen fluoride) / dichloromethane / 16 h / 20 °C 2: potassium tert-butylate / tetrahydrofuran / 1 h / 0 °C / Inert atmosphere 3: tetrabutyl ammonium fluoride / tetrahydrofuran / 3 h / 20 °C View Scheme

4α-acetoxy-2α-benzoyloxy-5β,20-epoxy-1β-hydroxy-9-oxo-10β-methoxy-7β,13α-di(triethylsilyloxy)-11-taxene (183133-98-4) → 4α-acetoxy-2α-benzoyloxy-5β,20-epoxy-1β,13α-dihydroxy-7β,10β-dimethoxy-9-oxo-11-taxene (183133-94-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: tetrabutyl ammonium fluoride / tetrahydrofuran / 0 - 5 °C / Inert atmosphere 2: sodium hydride / tetrahydrofuran / -5 - 0 °C 3: tetrabutyl ammonium fluoride / tetrahydrofuran / 0 - 5 °C / Inert atmosphere View Scheme
Multi-step reaction with 3 steps 1: tetrabutyl ammonium fluoride / tetrahydrofuran / 0 - 5 °C / Inert atmosphere 2: sodium hydride / -5 - 0 °C 3: tetrabutyl ammonium fluoride / tetrahydrofuran / 0 - 5 °C / Inert atmosphere View Scheme

7,10-di-O-1,3-dithian-2-yl-10-DAB (1432613-36-9) → 4α-acetoxy-2α-benzoyloxy-5β,20-epoxy-1β,13α-dihydroxy-7β,10β-dimethoxy-9-oxo-11-taxene (183133-94-0)

Conditions	Yield
With hydrogen In N,N-dimethyl-formamide at 50℃; under 8274.59 Torr; for 23h;

10-O-methyl-7-O-1,3-benzodithiolan-2-yl-10-DAB (1432613-43-8) → 4α-acetoxy-2α-benzoyloxy-5β,20-epoxy-1β,13α-dihydroxy-7β,10β-dimethoxy-9-oxo-11-taxene (183133-94-0)

Conditions	Yield
With hydrogen In N,N-dimethyl-formamide at 20℃; under 2584.17 Torr; for 15h;

C57H67NO15S4 (1432613-39-2) → 4α-acetoxy-2α-benzoyloxy-5β,20-epoxy-1β,13α-dihydroxy-7β,10β-dimethoxy-9-oxo-11-taxene (183133-94-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: methanol; sodium tetrahydroborate / tetrahydrofuran / 3 h / 20 °C 2: hydrogen / N,N-dimethyl-formamide / 23 h / 50 °C / 8274.59 Torr View Scheme

C37H48O10S4 (1432613-37-0) → 4α-acetoxy-2α-benzoyloxy-5β,20-epoxy-1β,13α-dihydroxy-7β,10β-dimethoxy-9-oxo-11-taxene (183133-94-0)

Conditions	Yield
With hydrogen In N,N-dimethyl-formamide at 20℃; under 2584.17 Torr; for 15h;

4α-acetoxy-2α-benzoyloxy-5β,20-epoxy-10β-methoxy-9-oxo-1β,13α,7β-trihydroxy-11-taxene (183133-97-3) → 4α-acetoxy-2α-benzoyloxy-5β,20-epoxy-1β,13α-dihydroxy-7β,10β-dimethoxy-9-oxo-11-taxene (183133-94-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: pyridine / dichloromethane / 20 °C 2: hydrogen / N,N-dimethyl-formamide / 15 h / 20 °C / 2584.17 Torr View Scheme

10-deacetylbaccatin III (32981-86-5) + MePhSO3Me → 4α-acetoxy-2α-benzoyloxy-5β,20-epoxy-1β,13α-dihydroxy-7β,10β-dimethoxy-9-oxo-11-taxene (183133-94-0)

Conditions	Yield
With caesium bromide; sodium hydride In tetrahydrofuran; N,N-dimethyl-formamide at -20 - 20℃; for 2.33333h; Inert atmosphere;

10-deacetylbaccatin III (32981-86-5) + methyl trifluoromethanesulphonate (99504-16-2) → 4α-acetoxy-2α-benzoyloxy-5β,20-epoxy-1β,13α-dihydroxy-7β,10β-dimethoxy-9-oxo-11-taxene (183133-94-0)

Conditions	Yield
With caesium bromide; sodium hydride In tetrahydrofuran; N,N-dimethyl-formamide at -20 - 20℃; for 2.33333h; Inert atmosphere;

carbazitaxel (183133-96-2) → 4α-acetoxy-2α-benzoyloxy-5β,20-epoxy-1β,13α-dihydroxy-7β,10β-dimethoxy-9-oxo-11-taxene (183133-94-0)

Conditions	Yield
With sodium hydroxide In water; acetonitrile at 20℃; for 0.5h; Further stages;

4α-acetoxy-2α-benzoyloxy-5β,20-epoxy-10β-methoxy-9-oxo-1β,13α,7β-trihydroxy-11-taxene (183133-97-3) + dimethyl sulfate (77-78-1) → 4α-acetoxy-2α-benzoyloxy-5β,20-epoxy-1β,13α-dihydroxy-7β,10β-dimethoxy-9-oxo-11-taxene (183133-94-0)

Conditions	Yield
With sodium hydride In N,N-dimethyl-formamide; mineral oil at -30℃; for 1h;

C43H48O14S2 + methylmagnesium bromide (75-16-1) → 4α-acetoxy-2α-benzoyloxy-5β,20-epoxy-1β,13α-dihydroxy-7β,10β-dimethoxy-9-oxo-11-taxene (183133-94-0)

Conditions	Yield
In tetrahydrofuran at 20℃; for 3h; Inert atmosphere;

4α-acetoxy-2α-benzoyloxy-5β,20-epoxy-1β,13α-dihydroxy-7β,10β-dimethoxy-9-oxo-11-taxene (183133-94-0) + (2R,4S,5R)-(2R,4S,5R)-3-tert-butoxycarbonyl-2-(4-methoxyphenyl)-4-phenyl-1,3-oxazolidine-5-carboxylic acid (155396-69-3) → 4α-acetoxy-2α-benzoyloxy-5β,20-epoxy-1β-hydroxy-7β,10β-dimethoxy-9-oxo-11-taxene-13α-yl (2R,4S,5R)-3-tert-butoxycarbonyl-2-(4-methoxyphenyl)-4-phenyl-1,3-oxazolidine-5-carboxylate (183133-95-1)

Conditions	Yield
With dmap; dicyclohexyl-carbodiimide In tetrahydrofuran at 20℃; for 2h;	91%
With dmap; dicyclohexyl-carbodiimide In tetrahydrofuran
With dmap; dicyclohexyl-carbodiimide In toluene at 20 - 30℃;
With dmap; dicyclohexyl-carbodiimide In ethyl acetate at 20℃; for 3h;

4α-acetoxy-2α-benzoyloxy-5β,20-epoxy-1β,13α-dihydroxy-7β,10β-dimethoxy-9-oxo-11-taxene (183133-94-0) + (2R,4S,5S)-3-tert-butoxycarbonyl-2-(4-methoxyphenyl)-4-phenyl-1,3-oxazolidine-5-carboxylic acid → 4α-acetoxy-2α-benzoyloxy-5β,20-epoxy-1β,13α-dihydroxy-7β,10β-dimethoxy-9-oxo-11-taxen-13α-yl (2R,4S,5S)-3-tert-butoxycarbonyl-2-(4-methoxyphenyl)-4-phenyl-1,3-oxazolidine-5-carboxylate

Conditions	Yield
Stage #1: 4α-acetoxy-2α-benzoyloxy-5β,20-epoxy-1β,13α-dihydroxy-7β,10β-dimethoxy-9-oxo-11-taxene; (2R,4S,5S)-3-tert-butoxycarbonyl-2-(4-methoxyphenyl)-4-phenyl-1,3-oxazolidine-5-carboxylic acid With dmap In tetrahydrofuran at 20 - 30℃; for 0.5h; Stage #2: With dicyclohexyl-carbodiimide In tetrahydrofuran Reagent/catalyst; Concentration; Temperature; Solvent;	82.5%

4α-acetoxy-2α-benzoyloxy-5β,20-epoxy-1β,13α-dihydroxy-7β,10β-dimethoxy-9-oxo-11-taxene (183133-94-0) + (2S,4S,5R)-3-tert-butoxycarbonyl-2-(4-methoxyphenyl)-4-phenyl-1,3-oxazolidine-5-carboxylic acid (157580-39-7) → 4α-acetoxy-2α-benzoyloxy-5β,20-epoxy-1β,13α-dihydroxy-7β,10β-dimethoxy-9-oxo-11-taxen-13α-yl-(2S,4S,5R)-3-tert-butoxycarbonyl-2-(4-methoxyphenyl)-4-phenyl-1,3-oxazolidine-5-carboxylate

Conditions	Yield
With dmap; diisopropyl-carbodiimide In tetrahydrofuran at 20 - 30℃; Reagent/catalyst; Solvent; Time; Temperature;	82.5%

4α-acetoxy-2α-benzoyloxy-5β,20-epoxy-1β,13α-dihydroxy-7β,10β-dimethoxy-9-oxo-11-taxene (183133-94-0) + tert-butyl (3R,4S)-2-oxo-4-phenyl-3-(triethylsilyloxy)azetidine-1-carboxylate (149198-47-0) → 1-hydroxy-7β,10β-di-methoxy-9-oxo-5β,20-epoxytax-11-ene-2α,4,13α-triyl 4-acetate 2-benzoate 13-{(2R,3S)-3-[(tert-butoxycarbonyl)amino]-2-trethylsilyloxy-3-phenylpropanoate} (1380584-07-5)

Conditions	Yield
With lithium hexamethyldisilazane In tetrahydrofuran; N,N-dimethyl-formamide at 20℃; for 1.58333h; Inert atmosphere;	80%
With iron(III) chloride; sodium hydride In tetrahydrofuran; mineral oil at -15 - 20℃; for 2.5h; Product distribution / selectivity; Inert atmosphere;	45%
With sodium hydride; lithium bromide In tetrahydrofuran at -15 - 20℃; for 2h; Inert atmosphere;

4α-acetoxy-2α-benzoyloxy-5β,20-epoxy-1β,13α-dihydroxy-7β,10β-dimethoxy-9-oxo-11-taxene (183133-94-0) + (4S,5R)-3-(2-furanylcarbonyl)-2-(4-methoxyphenyl)-4-phenyl-5-oxazolidinecarboxylic acid → C45H51NO14

Conditions	Yield
Stage #1: 4α-acetoxy-2α-benzoyloxy-5β,20-epoxy-1β,13α-dihydroxy-7β,10β-dimethoxy-9-oxo-11-taxene; (4S,5R)-3-(2-furanylcarbonyl)-2-(4-methoxyphenyl)-4-phenyl-5-oxazolidinecarboxylic acid With dmap; dicyclohexyl-carbodiimide In toluene at 70℃; for 1h; Stage #2: With hydrogenchloride In ethanol at 20℃; for 16h;	56%

4α-acetoxy-2α-benzoyloxy-5β,20-epoxy-1β,13α-dihydroxy-7β,10β-dimethoxy-9-oxo-11-taxene (183133-94-0) + (4S,5R)-3-(2-thienylcarbonyl)-2-(4-methoxyphenyl)-4-phenyl-5-oxazolidinecarboxylic acid → C45H51NO13S

Conditions	Yield
Stage #1: 4α-acetoxy-2α-benzoyloxy-5β,20-epoxy-1β,13α-dihydroxy-7β,10β-dimethoxy-9-oxo-11-taxene; (4S,5R)-3-(2-thienylcarbonyl)-2-(4-methoxyphenyl)-4-phenyl-5-oxazolidinecarboxylic acid With dmap; dicyclohexyl-carbodiimide In toluene at 70℃; for 1h; Stage #2: With hydrogenchloride In ethanol at 20℃; for 16h;	56%

4α-acetoxy-2α-benzoyloxy-5β,20-epoxy-1β,13α-dihydroxy-7β,10β-dimethoxy-9-oxo-11-taxene (183133-94-0) + (4S,5R)-3-(4-dimethylaminobenzoyl)-2-(4-methoxyphenyl)-4-phenyl-5-oxazolidinecarboxylic acid → C49H58N2O13

Conditions	Yield
Stage #1: 4α-acetoxy-2α-benzoyloxy-5β,20-epoxy-1β,13α-dihydroxy-7β,10β-dimethoxy-9-oxo-11-taxene; (4S,5R)-3-(4-dimethylaminobenzoyl)-2-(4-methoxyphenyl)-4-phenyl-5-oxazolidinecarboxylic acid With dmap; dicyclohexyl-carbodiimide In toluene at 70℃; for 1h; Stage #2: With hydrogenchloride In ethanol at 20℃; for 16h;	56%

4α-acetoxy-2α-benzoyloxy-5β,20-epoxy-1β,13α-dihydroxy-7β,10β-dimethoxy-9-oxo-11-taxene (183133-94-0) + C24H26N2O7 (1383325-08-3) → (2aR,4S,4aS,6R,9S,11S,12S,12aR,12bS)-12b-acetoxy-9-(((2R,3S)-2-((((benzyloxy)carbonyl)glycyl)oxy)-3-((tert-butoxycarbonyl)amino)-3-phenylpropanoyl)oxy)-11-hydroxy-4,6-dimethoxy-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]oxet-12-yl benzoate (1308398-68-6)

Conditions	Yield
With dmap; dicyclohexyl-carbodiimide In ethyl acetate at 20℃; Molecular sieve; Inert atmosphere;

4α-acetoxy-2α-benzoyloxy-5β,20-epoxy-1β,13α-dihydroxy-7β,10β-dimethoxy-9-oxo-11-taxene (183133-94-0) + tert-butyl (3R,4S)-2-oxo-4-phenyl-3-(triethylsilyloxy)azetidine-1-carboxylate (149198-47-0) → carbazitaxel (183133-96-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: lithium hexamethyldisilazane / N,N-dimethyl-formamide; tetrahydrofuran / 1.58 h / 20 °C / Inert atmosphere 2: toluene-4-sulfonic acid / tetrahydrofuran; methanol / 1 h / 0 - 5 °C View Scheme

4α-acetoxy-2α-benzoyloxy-5β,20-epoxy-1β,13α-dihydroxy-7β,10β-dimethoxy-9-oxo-11-taxene (183133-94-0) + C17H23NO5 → carbazitaxel (183133-96-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: lithium hexamethyldisilazane / N,N-dimethyl-formamide; tetrahydrofuran / 1.08 h / 20 °C / Inert atmosphere 2: toluene-4-sulfonic acid / butan-1-ol / 1 h / 50 °C View Scheme

4α-acetoxy-2α-benzoyloxy-5β,20-epoxy-1β,13α-dihydroxy-7β,10β-dimethoxy-9-oxo-11-taxene (183133-94-0) + C17H23NO5 → C48H63NO15

Conditions	Yield
With lithium hexamethyldisilazane In tetrahydrofuran; N,N-dimethyl-formamide at 20℃; for 1.08333h; Product distribution / selectivity; Inert atmosphere;

4α-acetoxy-2α-benzoyloxy-5β,20-epoxy-1β,13α-dihydroxy-7β,10β-dimethoxy-9-oxo-11-taxene (183133-94-0) → carbazitaxel (183133-96-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: dmap; dicyclohexyl-carbodiimide / tetrahydrofuran 2: water; hydrogenchloride / methanol / 20 °C View Scheme
Multi-step reaction with 2 steps 1: dmap / tetrahydrofuran / 0.5 h / 20 - 30 °C 2: hydrogenchloride / ethyl acetate / 0 °C View Scheme
Multi-step reaction with 2 steps 1: dmap; dicyclohexyl-carbodiimide / tetrahydrofuran / 2 h / 20 °C 2: hydrogenchloride / methanol; water; 2-methyltetrahydrofuran / 0.5 h / 20 °C View Scheme
Multi-step reaction with 3 steps 1: dicyclohexyl-carbodiimide; dmap / dichloromethane / 5 h / 60 °C 2: formic acid / 4 h / 20 °C 3: methanol / 14 h / 25 - 35 °C View Scheme
Multi-step reaction with 2 steps 1: dicyclohexyl-carbodiimide; dmap / ethyl acetate / 3 h / 20 °C 2: hydrogenchloride / dichloromethane; methanol; water / 1 h / 0 °C View Scheme

4α-acetoxy-2α-benzoyloxy-5β,20-epoxy-1β,13α-dihydroxy-7β,10β-dimethoxy-9-oxo-11-taxene (183133-94-0) → (αR, βS)-α-hydroxy-β-[[(1,1-dimethylethoxy)carbonyl]amino]benzene-propanoic acid (2aR,4S,4aS,6R,9S,11S,12S,12aR,12bS)-12b-(acetyloxy)-12-(benzoyloxy)-2a,3,4,4a,5,6,9,10,1112,12a,12b-dodecahydro-11-hydroxy-4,6-dimethoxy-4a,8,13,13-tetramethyl-5-oxo-7,11-methano-1H-cyclodeca[3,4]benz[1,2-b]oxet-9-yl ester isopropanol solvate (1402820-62-5)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: dmap / tetrahydrofuran / 0.5 h / 20 - 30 °C 2.1: hydrogenchloride / ethyl acetate / 0 °C 3.1: hydrogenchloride / methanol; water / 20 - 30 °C 3.2: 3.5 h / 0 - 30 °C View Scheme

Upstream product

• 32981-86-5 10-deacetylbaccatin III 
• 74-88-4 methyl iodide 
• 115437-18-8 7-triethylsilyl-10-deacetylbaccatin III 
• 183133-97-3 4α-acetoxy-2α-benzoyloxy-5β,20-epoxy-10β-methoxy-9-oxo-1β,13α,7β-trihydroxy-11-taxene 
• 160084-70-8 4α-acetoxy-2α-benzoyIoxy-5β,20-epoxy-1β,13α-dihydroxy-10β-methoxy-9-oxo-7β-triethylsilyloxy-11-taxene 
• 1432613-35-8 7,10-di-O-1,3-benzodithiolan-2-yl-10-DAB 
• 1432613-36-9 7,10-di-O-1,3-dithian-2-yl-10-DAB 
• 1432613-43-8 10-O-methyl-7-O-1,3-benzodithiolan-2-yl-10-DAB 
• 1432613-39-2 C₅₇H₆₇NO₁₅S₄ 
• 1432613-37-0 C₃₇H₄₈O₁₀S₄ 
• 333-27-7 methyl trifluoromethanesulfonate 
• 183133-96-2 carbazitaxel 
• 616-38-6 carbonic acid dimethyl ester 
• 75-16-1 methylmagnesium bromide 

Downstream Products

• 1380584-07-5 1-hydroxy-7β,10β-di-methoxy-9-oxo-5β,20-epoxytax-11-ene-2α,4,13α-triyl 4-acetate 2-benzoate 13-{(2R,3S)-3-[(tert-butoxycarbonyl)amino]-2-trethylsilyloxy-3-phenylpropanoate} 
• 1308398-68-6 (2aR,4S,4aS,6R,9S,11S,12S,12aR,12bS)-12b-acetoxy-9-(((2R,3S)-2-((((benzyloxy)carbonyl)glycyl)oxy)-3-((tert-butoxycarbonyl)amino)-3-phenylpropanoyl)oxy)-11-hydroxy-4,6-dimethoxy-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]oxet-12-yl benzoate 
• 183133-96-2 carbazitaxel 
• 183133-95-1 4α-acetoxy-2α-benzoyloxy-5β,20-epoxy-1β-hydroxy-7β,10β-dimethoxy-9-oxo-11-taxene-13α-yl (2R,4S,5R)-3-tert-butoxycarbonyl-2-(4-methoxyphenyl)-4-phenyl-1,3-oxazolidine-5-carboxylate 
• 1396601-24-3 4α-acetoxy-2α-benzoyloxy-5β,20-epoxy-1β-hydroxy-7β,10β-dimethoxy-9-oxo-13-(triethylsilyloxy)-11-taxene 
• 1402820-62-5 (αR, βS)-α-hydroxy-β-[[(1,1-dimethylethoxy)carbonyl]amino]benzene-propanoic acid (2aR,4S,4aS,6R,9S,11S,12S,12aR,12bS)-12b-(acetyloxy)-12-(benzoyloxy)-2a,3,4,4a,5,6,9,10,1112,12a,12b-dodecahydro-11-hydroxy-4,6-dimethoxy-4a,8,13,13-tetramethyl-5-oxo-7,11-methano-1H-cyclodeca[3,4]benz[1,2-b]oxet-9-yl ester isopropanol solvate 

Relevant articles and documents

Isolation, identification and characterization of potential impurities in cabazitaxel and their formation

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Cabazitaxel precursor derivative as well as synthesis method and application thereof

The invention discloses a preparation method of 7,10-dimethoxy-10-DAB (deacetyl baccatin) and a cabazitaxel precursor derivative as well as a synthesis method and application of the cabazitaxel precursor derivative. The synthesis method disclosed by the invention has the advantages of being easy in raw material obtaining, less in step, simple and convenient in purification and high in yield, and has the prospect of industrial production. The cabazitaxel precursor derivative synthetisedby the synthesis methoddisclosed by the invention has excellent antitumor activity and great application prospects.

Preparation method of 7beta,10beta-dimethoxy-10-deacetylbaccatin III

The invention relates to a preparation method of 7beta,10beta-dimethoxy-10-deacetylbaccatin III. Particularly, the method provided by the invention takes acetylbaccatin as a raw material and comprises a series of the following steps: protecting through silicon protecting groups at a 7 site and a 13 site; selectively removing the silicon protecting group at the 7 site; directly alkylating at the 7 site and a 10 site; and finally, removing the silicon protecting group at the 13 site to prepare a taxane compound, namely the 7beta,10beta-dimethoxy-10-deacetylbaccatin III shown as a formula V. (The formula V is shown in the description.).