114915-14-9

Basic information

• Product Name: Docetaxel intermediate
• Synonyms: DOCETAXEL INTERMEDIATE;INTERMEDIATE FOR DOCETAXEL;IntermediateIIIforDocetaxel;INTERMEDIATEOFDOCETAXEL;N-1 Step intermediate;(aR,bS)-beta-[[(1,1-Dimethylethoxy)carbonyl]amino]-alpha-hydroxy-benzenepropanoic acid (2aR,4S,4aS,6R,9S,11S,12S,12aR,12bS)-12b-(acetyloxy)-12-(benzoyloxy)-2a,3,4,4a,5,6,9,10,11,12,12a,12b-dodecahydro-11-hydroxy-4a,8,13,13-tetramethyl-5-oxo-4,6-bis[[(2,2,2-trichloroethoxy)carbonyl]oxy]-7,11-methano-1H-cyclodeca[3,4]benz[1,2-b]oxet-9-yl ester;7,10-Di Troc Docetaxel;Docetaxel InterMediate (N-1)
• CAS NO: 114915-14-9
• Molecular Formula: C₄₉H₅₅Cl₆NO₁₈
• Molecular Weight: 807.885
• EINECS: 1806241-263-5
• Mol File: 114915-14-9.mol
• Article Data: 12

Chemical Properties

• Boiling Point: 1064.656 °C at 760 mmHg
• Flash Point: 597.682 °C
• Appearance: /
• Density: 1.503 g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.607
• Storage Temp.: Sealed in dry,Room Temperature
• PKA: 11.20±0.46(Predicted)
• CAS DataBase Reference: Docetaxel intermediate(CAS DataBase Reference)
• NIST Chemistry Reference: Docetaxel intermediate(114915-14-9)
• EPA Substance Registry System: Docetaxel intermediate(114915-14-9)

Safety Data

• Hazardous Substances Data: 114915-14-9(Hazardous Substances Data)

Usage

General Description

Docetaxel intermediate is a chemical used in the production of the chemotherapy drug docetaxel, which is used to treat various types of cancer, including breast, prostate, and lung cancers. The intermediate is a key component in the synthesis of docetaxel and is responsible for the drug's anti-cancer properties. It is a potent microtubule inhibitor, meaning it disrupts the structure of the microtubules within cancer cells, preventing them from dividing and ultimately leading to cell death. The intermediate is a critical ingredient in the manufacture of docetaxel, allowing for the production of a high-quality and effective chemotherapy medication for the treatment of cancer.

InChI:InChI=1/C49H55Cl6NO18/c1-24-28(69-39(61)33(58)32(26-15-11-9-12-16-26)56-40(62)74-43(3,4)5)20-47(65)37(72-38(60)27-17-13-10-14-18-27)35-45(8,36(59)34(31(24)44(47,6)7)71-42(64)68-23-49(53,54)55)29(70-41(63)67-22-48(50,51)52)19-30-46(35,21-66-30)73-25(2)57/h9-18,28-30,32-35,37,58,65H,19-23H2,1-8H3,(H,56,62)/t28-,29-,30+,32-,33+,34+,35-,37-,45+,46-,47+/m0/s1

Synthetic route

13-[(2'R,4'S,5'R)-3'-t-butoxycarbonyl-2'-(1'''-naphthyl)-4'-phenyl-1,3-oxazolidine-5-carbonyl]-7,10-(di-2'',2'',2''-trichloroethoxy carbonyl)-10-deacetylbaccatin III (1033962-64-9) → 7,10-bis-O-(2,2,2-trichloroethoxycarbonyl)docetaxel (114915-14-9)

Conditions	Yield
Stage #1: 13-[(2'R,4'S,5'R)-3'-t-butoxycarbonyl-2'-(1'''-naphthyl)-4'-phenyl-1,3-oxazolidine-5-carbonyl]-7,10-(di-2'',2'',2''-trichloroethoxy carbonyl)-10-deacetylbaccatin III With toluene-4-sulfonic acid In chloroform at 20℃; for 3h; Stage #2: With water; sodium hydrogencarbonate In chloroform	88%
With methanol; toluene-4-sulfonic acid In chloroform at 20℃; for 3h;	88%

di-tert-butyl dicarbonate (24424-99-5) + 10-deacetyl-7,10-diTroc-baccatin III (114915-16-1) → 7,10-bis-O-(2,2,2-trichloroethoxycarbonyl)docetaxel (114915-14-9)

Conditions	Yield
With sodium hydrogencarbonate In tetrahydrofuran at 20℃;	87%
In water; ethyl acetate at 25 - 30℃; for 1h;
With sodium hydrogencarbonate In water at 55 - 65℃; for 2h;	737.4 g

di-tert-butyl dicarbonate (24424-99-5) + C44H45Cl6N3O16 (174729-13-6) → 7,10-bis-O-(2,2,2-trichloroethoxycarbonyl)docetaxel (114915-14-9)

Conditions	Yield
With potassium hydrogencarbonate; triphenylphosphine In dichloromethane; water for 19h; Ambient temperature;	63%

N-chloro-N-sodio-tert-butylcarbamate (73210-14-7) → 7,10-bis-O-(2,2,2-trichloroethoxycarbonyl)docetaxel (114915-14-9) + C49H55Cl6NO18 (114977-25-2) + C49H55Cl6NO18 (114915-26-3, 114977-26-3, 114977-27-4) + C49H55Cl6NO18 (114915-26-3, 114977-26-3, 114977-27-4)

Conditions	Yield
With osmium(VIII) oxide; silver nitrate In acetonitrile; tert-butyl alcohol for 24h; Ambient temperature; var. solvents and temp.; Further byproducts given;	A 25% B 22% C 21.5% D 16.5%

C57H61Cl6NO19 (859498-31-0) → 7,10-bis-O-(2,2,2-trichloroethoxycarbonyl)docetaxel (114915-14-9)

Conditions	Yield
With APTS In methanol at 20℃; for 16h;	25%
With toluene-4-sulfonic acid In methanol at 20℃;
With hydrogenchloride In water; ethyl acetate at 20 - 24℃; Solvent; Temperature;

N-chloro-N-sodio-tert-butylcarbamate (73210-14-7) → C44H46Cl6O17 (95603-47-7, 95672-97-2) + 7,10-bis-O-(2,2,2-trichloroethoxycarbonyl)docetaxel (114915-14-9) + C49H55Cl6NO18 (114977-25-2) + C49H55Cl6NO18 (114915-26-3, 114977-26-3, 114977-27-4)

Conditions	Yield
With osmium(VIII) oxide; silver nitrate In toluene; tert-butyl alcohol at 4℃; for 24h; var. solvents and temp.; Further byproducts given;	A 12% B 20% C 17% D 18%

methyl (2S,3R)-3-phenyl-2,3-dihydroxypropanoate (124649-67-8) → 7,10-bis-O-(2,2,2-trichloroethoxycarbonyl)docetaxel (114915-14-9)

Conditions

Yield

Multi-step reaction with 6 steps 1: triethylamine / CH2Cl2 / 38 h / 0 °C 2: K2CO3 / dimethylformamide; H2O / 24 h / Ambient temperature 3: 80 percent / LiOH*H2O / methanol; H2O / 1 h / Ambient temperature 4: 91 percent / dicyclohexylcarbodiimide, 4-N,N-dimethylaminopyridine / toluene / 1 h / 80 °C 5: 78 percent / sodium azide, methyl formate / methanol; H2O / 40 h / 50 °C / other reagent: tri-n-butyltinazide/ZnI2 6: 63 percent / KHCO3, PPh3 / CH2Cl2; H2O / 19 h / Ambient temperature View Scheme

(2S,3R)-(-)-methyl 3-hydroxy-3-phenyl-2-((p-tolylsulfonyl)oxy)propionate (124605-43-2) → 7,10-bis-O-(2,2,2-trichloroethoxycarbonyl)docetaxel (114915-14-9)

Conditions

Yield

Multi-step reaction with 5 steps 1: K2CO3 / dimethylformamide; H2O / 24 h / Ambient temperature 2: 80 percent / LiOH*H2O / methanol; H2O / 1 h / Ambient temperature 3: 91 percent / dicyclohexylcarbodiimide, 4-N,N-dimethylaminopyridine / toluene / 1 h / 80 °C 4: 78 percent / sodium azide, methyl formate / methanol; H2O / 40 h / 50 °C / other reagent: tri-n-butyltinazide/ZnI2 5: 63 percent / KHCO3, PPh3 / CH2Cl2; H2O / 19 h / Ambient temperature View Scheme

(2R,3R)-(+)-methyl 3-phenyloxiranecarboxylate (99528-65-1) → 7,10-bis-O-(2,2,2-trichloroethoxycarbonyl)docetaxel (114915-14-9)

Conditions	Yield
Multi-step reaction with 4 steps 1: 80 percent / LiOH*H2O / methanol; H2O / 1 h / Ambient temperature 2: 91 percent / dicyclohexylcarbodiimide, 4-N,N-dimethylaminopyridine / toluene / 1 h / 80 °C 3: 78 percent / sodium azide, methyl formate / methanol; H2O / 40 h / 50 °C / other reagent: tri-n-butyltinazide/ZnI2 4: 63 percent / KHCO3, PPh3 / CH2Cl2; H2O / 19 h / Ambient temperature View Scheme

methyl (2R,3S)-3-phenylglycidate (115794-67-7) → 7,10-bis-O-(2,2,2-trichloroethoxycarbonyl)docetaxel (114915-14-9)

Conditions

Yield

Multi-step reaction with 5 steps 1: NaOH / tetrahydrofuran; H2O / 0.33 h / Ambient temperature 2: 5.55 g / dicyclohexylcarbodiimide, 4-N,N-dimethylaminopyridine / toluene / 0.17 h / Ambient temperature 3: 76 percent / hexamethylphosphoramide, TiBr4 / CH2Cl2 / 18 h / 0 °C 4: 71 percent / sodium azide, 15-crown-5 / dimethylformamide / 18 h / 0 °C 5: 63 percent / KHCO3, PPh3 / CH2Cl2; H2O / 19 h / Ambient temperature View Scheme

Methyl cinnamate (103-26-4) + XCH2CO2Et → 7,10-bis-O-(2,2,2-trichloroethoxycarbonyl)docetaxel (114915-14-9)

Conditions

Yield

Multi-step reaction with 7 steps 1: 65 percent / AD-mix-β / 2-methyl-propan-2-ol; H2O / 18 h / Ambient temperature 2: triethylamine / CH2Cl2 / 38 h / 0 °C 3: K2CO3 / dimethylformamide; H2O / 24 h / Ambient temperature 4: 80 percent / LiOH*H2O / methanol; H2O / 1 h / Ambient temperature 5: 91 percent / dicyclohexylcarbodiimide, 4-N,N-dimethylaminopyridine / toluene / 1 h / 80 °C 6: 78 percent / sodium azide, methyl formate / methanol; H2O / 40 h / 50 °C / other reagent: tri-n-butyltinazide/ZnI2 7: 63 percent / KHCO3, PPh3 / CH2Cl2; H2O / 19 h / Ambient temperature View Scheme

cis-2,3-epoxy-3-phenyl-1-propanoic acid (99528-64-0) → 7,10-bis-O-(2,2,2-trichloroethoxycarbonyl)docetaxel (114915-14-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: 91 percent / dicyclohexylcarbodiimide, 4-N,N-dimethylaminopyridine / toluene / 1 h / 80 °C 2: 78 percent / sodium azide, methyl formate / methanol; H2O / 40 h / 50 °C / other reagent: tri-n-butyltinazide/ZnI2 3: 63 percent / KHCO3, PPh3 / CH2Cl2; H2O / 19 h / Ambient temperature View Scheme

C44H44Cl6O16 (174847-58-6) → 7,10-bis-O-(2,2,2-trichloroethoxycarbonyl)docetaxel (114915-14-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: 76 percent / hexamethylphosphoramide, TiBr4 / CH2Cl2 / 18 h / 0 °C 2: 71 percent / sodium azide, 15-crown-5 / dimethylformamide / 18 h / 0 °C 3: 63 percent / KHCO3, PPh3 / CH2Cl2; H2O / 19 h / Ambient temperature View Scheme

13-O-((2R,3R)-3-phenylglycidoyl)-7,10-O,O'-bis(2,2,2-trichloroethoxycarbonyl)-10-deacetylbaccatin (174729-12-5) → 7,10-bis-O-(2,2,2-trichloroethoxycarbonyl)docetaxel (114915-14-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: 78 percent / sodium azide, methyl formate / methanol; H2O / 40 h / 50 °C / other reagent: tri-n-butyltinazide/ZnI2 2: 63 percent / KHCO3, PPh3 / CH2Cl2; H2O / 19 h / Ambient temperature View Scheme

13-O-((2S,3R)-3-bromo-2-hydroxy-3-phenylpropionyl)-7,10-O,O'-bis(2,2,2-trichloroethoxycarbonyl)-10-deacetylbaccatin (174729-14-7) → 7,10-bis-O-(2,2,2-trichloroethoxycarbonyl)docetaxel (114915-14-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: 71 percent / sodium azide, 15-crown-5 / dimethylformamide / 18 h / 0 °C 2: 63 percent / KHCO3, PPh3 / CH2Cl2; H2O / 19 h / Ambient temperature View Scheme

(2R,3S)-3-phenyloxiranecarboxylic acid (79898-19-4) → 7,10-bis-O-(2,2,2-trichloroethoxycarbonyl)docetaxel (114915-14-9)

Conditions	Yield
Multi-step reaction with 4 steps 1: 5.55 g / dicyclohexylcarbodiimide, 4-N,N-dimethylaminopyridine / toluene / 0.17 h / Ambient temperature 2: 76 percent / hexamethylphosphoramide, TiBr4 / CH2Cl2 / 18 h / 0 °C 3: 71 percent / sodium azide, 15-crown-5 / dimethylformamide / 18 h / 0 °C 4: 63 percent / KHCO3, PPh3 / CH2Cl2; H2O / 19 h / Ambient temperature View Scheme

(2R,3S)-3-amino-2-hydroxy-3-phenylpropionic acid ethyl ester (143615-00-3) → 7,10-bis-O-(2,2,2-trichloroethoxycarbonyl)docetaxel (114915-14-9)

Conditions	Yield
Multi-step reaction with 6 steps 1: 76 percent / NaHCO3 / CH2Cl2 / 20 °C 2: 99 percent / pyridinium paratoluenesulfonate (PTSP) / toluene / 80 °C 3: 100 percent / LiOH, H2O / ethanol / 20 °C 4: 98 percent / DCC, DMAP / toluene / 2 h / 80 °C 5: 78 percent / HCOOH / 4 h / 20 °C 6: 87 percent / NaHCO3 / tetrahydrofuran / 20 °C View Scheme

(2R,3S)-3-azido-2-hydroxy-benzenepropanoic acid ethyl ester (144787-20-2) → 7,10-bis-O-(2,2,2-trichloroethoxycarbonyl)docetaxel (114915-14-9)

Conditions

Yield

Multi-step reaction with 7 steps 1: 86 percent / H2 / 10percent Pd/C / ethyl acetate / 760 Torr 2: 76 percent / NaHCO3 / CH2Cl2 / 20 °C 3: 99 percent / pyridinium paratoluenesulfonate (PTSP) / toluene / 80 °C 4: 100 percent / LiOH, H2O / ethanol / 20 °C 5: 98 percent / DCC, DMAP / toluene / 2 h / 80 °C 6: 78 percent / HCOOH / 4 h / 20 °C 7: 87 percent / NaHCO3 / tetrahydrofuran / 20 °C View Scheme

benzaldehyde (100-52-7) + aminoguanidine salt → 7,10-bis-O-(2,2,2-trichloroethoxycarbonyl)docetaxel (114915-14-9)

Conditions

Yield

Multi-step reaction with 10 steps 1: 1.) Et3N, Bu2BOTf / 1.) CH2Cl2, -70 to 20 deg C, 2 h, 2.) -78 to 0 deg C, 1 h 2: 81 percent / tetrahydrofuran / 0.25 h / -75 - 15 °C 3: 99 percent / NaN3, NH4Cl / ethanol / 8 h / 60 °C 4: 86 percent / H2 / 10percent Pd/C / ethyl acetate / 760 Torr 5: 76 percent / NaHCO3 / CH2Cl2 / 20 °C 6: 99 percent / pyridinium paratoluenesulfonate (PTSP) / toluene / 80 °C 7: 100 percent / LiOH, H2O / ethanol / 20 °C 8: 98 percent / DCC, DMAP / toluene / 2 h / 80 °C 9: 78 percent / HCOOH / 4 h / 20 °C 10: 87 percent / NaHCO3 / tetrahydrofuran / 20 °C View Scheme

7,10-di-(2,2,2-trichloroethyloxycarbonyl)-10-deacetylbaccatin III (95603-44-4) → 7,10-bis-O-(2,2,2-trichloroethoxycarbonyl)docetaxel (114915-14-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: 98 percent / DCC, DMAP / toluene / 2 h / 80 °C 2: 78 percent / HCOOH / 4 h / 20 °C 3: 87 percent / NaHCO3 / tetrahydrofuran / 20 °C View Scheme
Multi-step reaction with 2 steps 1: dmap; dicyclohexyl-carbodiimide / toluene / 50 °C 2: sodium carbonate; dihydrogen peroxide / water; tetrahydrofuran / 20 °C View Scheme
Multi-step reaction with 3 steps 1: dmap; dicyclohexyl-carbodiimide / toluene / 50 °C 2: sodium carbonate; dihydrogen peroxide / water; tetrahydrofuran / 20 °C 3: triphenylphosphine; diethylazodicarboxylate; 4-nitro-benzoic acid / tetrahydrofuran View Scheme

ethyl (2R,3R)-3-phenyl-2,3-oxiranepropanoate (126060-73-9) → 7,10-bis-O-(2,2,2-trichloroethoxycarbonyl)docetaxel (114915-14-9)

Conditions

Yield

Multi-step reaction with 8 steps 1: 99 percent / NaN3, NH4Cl / ethanol / 8 h / 60 °C 2: 86 percent / H2 / 10percent Pd/C / ethyl acetate / 760 Torr 3: 76 percent / NaHCO3 / CH2Cl2 / 20 °C 4: 99 percent / pyridinium paratoluenesulfonate (PTSP) / toluene / 80 °C 5: 100 percent / LiOH, H2O / ethanol / 20 °C 6: 98 percent / DCC, DMAP / toluene / 2 h / 80 °C 7: 78 percent / HCOOH / 4 h / 20 °C 8: 87 percent / NaHCO3 / tetrahydrofuran / 20 °C View Scheme

(2R,3S) ethyl N-(t-butoxycarbonyl)-3-phenylisoserine (143527-75-7) → 7,10-bis-O-(2,2,2-trichloroethoxycarbonyl)docetaxel (114915-14-9)

Conditions	Yield
Multi-step reaction with 5 steps 1: 99 percent / pyridinium paratoluenesulfonate (PTSP) / toluene / 80 °C 2: 100 percent / LiOH, H2O / ethanol / 20 °C 3: 98 percent / DCC, DMAP / toluene / 2 h / 80 °C 4: 78 percent / HCOOH / 4 h / 20 °C 5: 87 percent / NaHCO3 / tetrahydrofuran / 20 °C View Scheme

(4S,5R)-3-(tert-butoxycarbonyl)-2,2-dimethyl-4-phenyloxazolidine-5-carboxylic acid (143615-03-6, 143527-70-2) → 7,10-bis-O-(2,2,2-trichloroethoxycarbonyl)docetaxel (114915-14-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: 98 percent / DCC, DMAP / toluene / 2 h / 80 °C 2: 78 percent / HCOOH / 4 h / 20 °C 3: 87 percent / NaHCO3 / tetrahydrofuran / 20 °C View Scheme

ethyl (4S,5R)-3-tert-butoxycarbonyl-2,2-dimethyl-4-phenyl-5-oxazolidinecarboxylate (143527-74-6) → 7,10-bis-O-(2,2,2-trichloroethoxycarbonyl)docetaxel (114915-14-9)

Conditions	Yield
Multi-step reaction with 4 steps 1: 100 percent / LiOH, H2O / ethanol / 20 °C 2: 98 percent / DCC, DMAP / toluene / 2 h / 80 °C 3: 78 percent / HCOOH / 4 h / 20 °C 4: 87 percent / NaHCO3 / tetrahydrofuran / 20 °C View Scheme

(4S,5R)-3-((2S,3R)-2-Bromo-3-hydroxy-3-phenyl-propionyl)-4-methyl-5-phenyl-oxazolidin-2-one (144704-63-2) → 7,10-bis-O-(2,2,2-trichloroethoxycarbonyl)docetaxel (114915-14-9)

Conditions

Yield

Multi-step reaction with 9 steps 1: 81 percent / tetrahydrofuran / 0.25 h / -75 - 15 °C 2: 99 percent / NaN3, NH4Cl / ethanol / 8 h / 60 °C 3: 86 percent / H2 / 10percent Pd/C / ethyl acetate / 760 Torr 4: 76 percent / NaHCO3 / CH2Cl2 / 20 °C 5: 99 percent / pyridinium paratoluenesulfonate (PTSP) / toluene / 80 °C 6: 100 percent / LiOH, H2O / ethanol / 20 °C 7: 98 percent / DCC, DMAP / toluene / 2 h / 80 °C 8: 78 percent / HCOOH / 4 h / 20 °C 9: 87 percent / NaHCO3 / tetrahydrofuran / 20 °C View Scheme

4-acetoxy-2α-benzoyloxy-5β,20-epoxy-1-hydroxy-9-oxo-7β,10β-bis[(2,2,2-tri-chloroethoxy)carbonyloxy]-11-taxen-13α-yl (4S,5R)-3-tert-butoxycarbonyl-2,2-dimethyl-4-phenyl-5-oxazolidinecarboxylate (143527-76-8) → 7,10-bis-O-(2,2,2-trichloroethoxycarbonyl)docetaxel (114915-14-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: 78 percent / HCOOH / 4 h / 20 °C 2: 87 percent / NaHCO3 / tetrahydrofuran / 20 °C View Scheme
Multi-step reaction with 2 steps 1: formic acid / 1 h / 25 - 35 °C 2: sodium hydrogencarbonate / water / 2 h / 55 - 65 °C View Scheme

(3'S)-7,10-di-Troc-docetaxel → (2'R,3'S)-7,10-di-Troc-docetaxel (151636-78-1) + 7,10-bis-O-(2,2,2-trichloroethoxycarbonyl)docetaxel (114915-14-9)

Conditions	Yield
With silica gel column (20 μM, 0.45*90 cm) In methanol; dichloromethane Purification / work up; Resolution of diastereomeric mixture;

(2'R,3'S)-7,10-di-Troc-docetaxel (151636-78-1) → 7,10-bis-O-(2,2,2-trichloroethoxycarbonyl)docetaxel (114915-14-9)

Conditions	Yield
Stage #1: (2'R,3'S)-7,10-di-Troc-docetaxel With triphenylphosphine; diethylazodicarboxylate; 4-nitro-benzoic acid In tetrahydrofuran Stage #2: With potassium hydroxide In tetrahydrofuran
Stage #1: (2'R,3'S)-7,10-di-Troc-docetaxel With triphenylphosphine; diethylazodicarboxylate; 4-nitro-benzoic acid In tetrahydrofuran Stage #2: With potassium hydroxide In tetrahydrofuran

(3'S)-2'-Ac-7,10-di-Troc-docetaxel → 7,10-bis-O-(2,2,2-trichloroethoxycarbonyl)docetaxel (114915-14-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium carbonate; dihydrogen peroxide / water; tetrahydrofuran / 20 °C 2: triphenylphosphine; diethylazodicarboxylate; 4-nitro-benzoic acid / tetrahydrofuran View Scheme

(3'S)-2'-Ac-7,10-di-Troc-docetaxel → (2'R,3'S)-7,10-di-Troc-docetaxel (151636-78-1) + 7,10-bis-O-(2,2,2-trichloroethoxycarbonyl)docetaxel (114915-14-9)

Conditions	Yield
With dihydrogen peroxide; sodium carbonate In tetrahydrofuran; water at 20℃;

7,10-bis-O-(2,2,2-trichloroethoxycarbonyl)docetaxel (114915-14-9) + N,N'-dimethyl-N-benzyl-[4-(2,3,4-tri-O-tert-butyldimethylsilyl-β-D-glucopyranosyl)uronate-3-nitrobenzoyloxycarbonyl]ethylenediamine carbamoyl chloride (637330-41-7) → C93H126Cl6N4O30Si3

Conditions	Yield
With dmap In dichloromethane for 2h;	93%

7,10-bis-O-(2,2,2-trichloroethoxycarbonyl)docetaxel (114915-14-9) → Docetaxel (114915-20-7, 114977-28-5, 114977-29-6, 133577-32-9, 133577-33-0)

Conditions	Yield
With acetic acid; zinc In methanol at 60℃; for 2h;	90%
With acetic acid; zinc In methanol at 60℃; for 1h;	90%
Product distribution / selectivity;	90%

7,10-bis-O-(2,2,2-trichloroethoxycarbonyl)docetaxel (114915-14-9) → 10-deacetyl-7,10-diTroc-baccatin III (114915-16-1)

Conditions	Yield
With trimethylsilyl iodide In acetonitrile at 0℃; for 0.5h;	75%
With formic acid at 18℃; for 1.5h; Temperature;	25.3 g

glutaric anhydride, (108-55-4) + 7,10-bis-O-(2,2,2-trichloroethoxycarbonyl)docetaxel (114915-14-9) → C54H61Cl6NO21

Conditions	Yield
With pyridine at -20 - 25℃;	60%

Upstream product

• 100-52-7 benzaldehyde 
• 157240-36-3 (2R,3S)-3-phenylisoserine methyl ester 
• 124605-42-1 methyl (2R,3S)-3-(tert-butoxycarbonylamino)-2-hydroxy-3-phenylpropionate 
• 24424-99-5 di-tert-butyl dicarbonate 
• 670254-71-4 (2*,4S,5R)-methyl N-tert-butoxycarbonyl-2-(4'-methoxy)phenyl-4-phenyl-1,3-oxazolidine-5-methionate 
• 196404-55-4 acide (4S,5R)-N-(tert-butoxycarbonyl)-2-(4-O-methoxyphenyl)-4-phenyl-5-oxazolidine carboxylique 
• 144787-20-2 (2R,3S)-3-azido-2-hydroxy-benzenepropanoic acid ethyl ester 
• 143615-00-3 (2R,3S)-3-amino-3-phenyl-2-hydroxypropionic acid ethyl ester 
• 79898-19-4 (2R,3S)-3-phenyloxiranecarboxylic acid 
• 174729-14-7 13-O-((2S,3R)-3-bromo-2-hydroxy-3-phenylpropionyl)-7,10-O,O'-bis(2,2,2-trichloroethoxycarbonyl)-10-deacetylbaccatin 
• 174729-12-5 13-O-((2R,3R)-3-phenylglycidoyl)-7,10-O,O'-bis(2,2,2-trichloroethoxycarbonyl)-10-deacetylbaccatin 
• 174847-58-6 C₄₄H₄₄Cl₆O₁₆ 
• 99528-64-0 cis-2,3-epoxy-3-phenyl-1-propanoic acid 
• 103-26-4 Methyl cinnamate 

Downstream Products

• 78479-12-6 10-deacetyltaxol B 
• 114915-20-7 Docetaxel 
• 114915-16-1 10-deacetyl-7,10-diTroc-baccatin III 
• 114915-18-3 C₅₁H₅₁Cl₆NO₁₇ 
• 78432-77-6 10-deacetylpaclitaxel 

Relevant articles and documents

Semisynthesis method for docetaxel

The invention relates to a semisynthesis method for docetaxel. The semisynthesis method comprises the following steps: protecting hydroxyl groups on 7-carbon and 10-carbon on 10-DAB III by using chloroformic acid-2,2,2-trichloroethyl ester so as to obtain an intermediate I, performing a condensation reaction on the intermediate I and a five-membered ring side chain so as to obtain an intermediateII, performing ring opening on the intermediate II under the action of hydrochloric acid to remove a protecting group on the five-membered ring side chain so as to obtain an intermediate III, and removing a Troc protecting group from the intermediate III under an acidic condition so as to obtain the docetaxel. The semisynthesis method provided by the invention has the advantages of simple processroute, mild reaction conditions, fewer impurities generated in the reaction process, higher yield and stable properties of obtained intermediates, and applicability to industrial large-scale production.

Docetaxel side chain 2'-derived novel taxanes antitumor compound as well as synthesis method and application thereof

The invention discloses a docetaxel side chain 2'-derived novel taxanes antitumor compound shown as the general structure formula (I) as well as a synthesis method and application thereof. In the formula, X is N or O, R is H or acetyl, and R' is H, nitryl, cyano, methoxyl or a halogen group. The synthesis method takes 10-deacetylbaccatin is used as a raw material; after 7-OH and 10-OH are protected, condensation with phenylisoserine (side chain) protecting 3'-NHBoc and 2'-OH in the presence of condensation agents DCC (Dicyclohexylcarbodiimide) and DMAP (Dimethylaminopyridine) is performed; esterification with substituted phenyl isoxazole carboxylic acid or substituted phenyl oxadiazole methyl carboxylic acid in the presence of the DCC and the DMAP is performed; finally, a protecting group is removed to obtain the compound. The compound disclosed by the invention has relatively high activity on tumor cells.

METHOD FOR PREPARING TAXANE DERIVATIVES

Provided is a method for preparing a taxane derivative, comprising: carrying out condensation of a phenylisoserine derivatives having a protective group introduced thereto or a mixture of isomers thereof, as a side chain, with a baccatin III derivative or 10-deacetyl-baccatin III derivative to obtain a mixture of isomers; separating the isomers via chromatography; and carrying out a selective reversion of the stereochemical structure of a separated isomer, which is suitable for producing a taxane derivative in a large scale with high yield.