32981-85-4

Basic information

• Product Name: Methyl (2R,3S)-3-(benzoylamino)-2-hydroxy-3-phenylpropanoate
• Synonyms: PACLITAXEL SIDE CHAIN 4;PACLITAXEL SIDE CHAIN NO 4;C-13 SIDE CHAIN FOR PACLITAXEL II;(2R,3S)-1-Benzoyl-2-Hydroxy-3-Aminophenylpionic Acid Ester;METHYL (2R,3S)-3-BENZAMIDO-2-HYDRO-3-PHENYLPROPIONATE;METHYL (2R,3S)-3-BENZAMIDO-2-HYDROXY-3-PHENYLPROPIONATE;N-BENZOYL-(2R,3S)-3-PHENYLISOSERINE METHYL ESTER;PACLITAXE SIDE CHIAN 4
• CAS NO: 32981-85-4
• Molecular Formula: C₁₇H₁₇NO₄
• Molecular Weight: 299.32
• EINECS: 1806241-263-5
• Product Categories: CHIRAL CHEMICALS;Intermediates
• Mol File: 32981-85-4.mol
• Article Data: 55

Chemical Properties

• Melting Point: 178-183℃
• Boiling Point: 540.3 °C at 760 mmHg
• Flash Point: 280.6 °C
• Appearance: White/Crystalline Powder
• Density: 1.236 g/cm³
• Vapor Pressure: 1.66E-12mmHg at 25°C
• Refractive Index: 1.588
• Storage Temp.: Sealed in dry,Room Temperature
• Solubility: DMSO (Slightly), Ethyl Acetate (Slightly, Heated), Methanol (Slightly)
• PKA: 12.05±0.20(Predicted)
• CAS DataBase Reference: Methyl (2R,3S)-3-(benzoylamino)-2-hydroxy-3-phenylpropanoate(CAS DataBase Reference)
• NIST Chemistry Reference: Methyl (2R,3S)-3-(benzoylamino)-2-hydroxy-3-phenylpropanoate(32981-85-4)
• EPA Substance Registry System: Methyl (2R,3S)-3-(benzoylamino)-2-hydroxy-3-phenylpropanoate(32981-85-4)

Safety Data

• Hazardous Substances Data: 32981-85-4(Hazardous Substances Data)

Usage

Chemical Properties

white crystal powder

Uses

(2R,3S)-N-Benzoyl-3-phenyl Isoserine Methyl Ester is an intermediate in the preparation of potent anticancer drug Paclitaxel (P132500) used to study the location of the binding sites.

InChI:InChI=1/C17H17NO4/c1-22-17(21)15(19)14(12-8-4-2-5-9-12)18-16(20)13-10-6-3-7-11-13/h2-11,14-15,19H,1H3,(H,18,20)/t14-,15+/m0/s1

Synthetic route

methyl (2R,3S)-3-benzoylamino-2-benzyloxy-3-phenylpropanethioate (145041-37-8) → methyl (2R,3S)-3-benzoylamino-2-hydroxy-3-phenylpropanoate (32981-85-4)

Conditions	Yield
With palladium on activated charcoal; hydrogen In methanol under 4654.46 Torr;	100%
With hydrogen; 1% Pd/C In methanol under 4654.46 Torr;	100%
With hydrogenchloride; hydrogen; palladium on activated charcoal In ethanol at 60℃; for 1h;	78%
With hydrogen; palladium on activated charcoal In ethanol at 60℃;	78%

Methyl (2R,3S)-(+)-2-hydroxy-3-azido-3-phenyl-propionate (99458-15-8) + benzoyl chloride (98-88-4) → methyl (2R,3S)-3-benzoylamino-2-hydroxy-3-phenylpropanoate (32981-85-4)

Conditions	Yield
Stage #1: Methyl (2R,3S)-(+)-2-hydroxy-3-azido-3-phenyl-propionate; benzoyl chloride With dmap; triethylamine In ethyl acetate at 20℃; for 4h; Stage #2: With hydrogen; palladium on activated charcoal In methanol; ethyl acetate for 48h; Further stages.;	92%
Stage #1: Methyl (2R,3S)-(+)-2-hydroxy-3-azido-3-phenyl-propionate; benzoyl chloride With dmap; triethylamine In methanol; ethyl acetate at 20℃; for 7h; Stage #2: With hydrogen; palladium on activated carbon In methanol; ethyl acetate for 48h;	92%
Stage #1: Methyl (2R,3S)-(+)-2-hydroxy-3-azido-3-phenyl-propionate; benzoyl chloride; dmap In methanol; ethyl acetate at 20℃; for 7h; Stage #2: With hydrogen; palladium 10% on activated carbon In methanol; ethyl acetate for 48h;	88%

methyl (2R,3S)-2-acetoxy-3-phenyl-3-benzoylaminopropanoate (146848-86-4) → methyl (2R,3S)-3-benzoylamino-2-hydroxy-3-phenylpropanoate (32981-85-4)

Conditions	Yield
With sodium methylate In methanol at 20℃; for 1h;	92%

(4S,5R)-2,4-diphenyl-2-oxazoline-5-carboxylic acid methyl ester (146848-91-1) → methyl (2R,3S)-3-benzoylamino-2-hydroxy-3-phenylpropanoate (32981-85-4)

Conditions	Yield
With hydrogenchloride In methanol for 2h; Heating;	90%
With hydrogenchloride In methanol for 5h; Heating;	85%
With hydrogenchloride In methanol for 5h; Heating;	85%

diazomethane (186581-53-3, 908094-01-9) + (2R,3S)-N-benzoyl-3-phenylisoserine (132201-33-3) → methyl (2R,3S)-3-benzoylamino-2-hydroxy-3-phenylpropanoate (32981-85-4)

Conditions	Yield
In tetrahydrofuran; diethyl ether	90%
In methanol; diethyl ether

(2R,3S)-(+)-methyl 3-azido-2-benzoly-3-phenylpropionate (99458-16-9) → methyl (2R,3S)-3-benzoylamino-2-hydroxy-3-phenylpropanoate (32981-85-4)

Conditions	Yield
With hydrogen; palladium on activated charcoal In methanol	88%
With hydrogen; toluene-4-sulfonic acid; palladium on activated charcoal	76%
With hydrogen; palladium on activated charcoal In methanol under 2585.7 Torr; for 4h;	74%
With hydrogen; palladium on activated charcoal In methanol at 20℃; under 760 Torr; for 48h;	71%
With hydrogen; palladium on activated charcoal 1.) CH3OH, 15 h, 2.) CH3OH, RT, 72 h; Yield given. Multistep reaction;

methanol (67-56-1) + benzoyl chloride (98-88-4) + (2R,3S)-3-acetylamino-2-hydroxy-3-phenylpropanoic acid isopropyl ester (195624-97-6) → methyl (2R,3S)-3-benzoylamino-2-hydroxy-3-phenylpropanoate (32981-85-4)

Conditions	Yield
Stage #1: methanol; (2R,3S)-3-acetylamino-2-hydroxy-3-phenylpropanoic acid isopropyl ester With hydrogenchloride for 20h; Heating; Stage #2: benzoyl chloride With triethylamine In dichloromethane at 0 - 20℃;	88%

methanol (67-56-1) + benzoyl chloride (98-88-4) + (2R,3S)-3-phenylisoserine hydrochloride (132201-32-2) → methyl (2R,3S)-3-benzoylamino-2-hydroxy-3-phenylpropanoate (32981-85-4)

Conditions	Yield
Stage #1: benzoyl chloride; (2R,3S)-3-phenylisoserine hydrochloride With sodium hydroxide In water at 20℃; for 1h; pH=9 - 12; Stage #2: methanol Concentration;	85.6%

methanol (67-56-1) + benzyl chloride (100-44-7) + (2R,3S)-3-acetylamino-2-hydroxy-3-phenylpropanoic acid isopropyl ester (195624-97-6) → methyl (2R,3S)-3-benzoylamino-2-hydroxy-3-phenylpropanoate (32981-85-4)

Conditions	Yield
Stage #1: methanol; (2R,3S)-3-acetylamino-2-hydroxy-3-phenylpropanoic acid isopropyl ester With hydrogenchloride for 20h; Addition; Heating; Stage #2: benzyl chloride With triethylamine In dichloromethane at 0 - 20℃; for 2h; Substitution; Further stages.;	85%

methyl (2S,3S)-3-benzoylamino-2-hydroxy-3-phenylpropanoate (144541-45-7) → methyl (2R,3S)-3-benzoylamino-2-hydroxy-3-phenylpropanoate (32981-85-4)

Conditions	Yield
With thionyl chloride In dichloromethane for 5h; Inert atmosphere; Reflux;	85%
Multi-step reaction with 2 steps 1.1: SOCl2 / CH2Cl2 / Heating 2.1: HCl / H2O; methanol / Heating 2.2: NaHCO3 / H2O; methanol / 50 °C View Scheme
Multi-step reaction with 2 steps 1: 90 percent / DEAD; PPh3 / benzene / 20 h / 20 °C 2: 90 percent / 1N aq. HCl / methanol / 2 h / Heating View Scheme
Multi-step reaction with 2 steps 1: 77 percent / Ph3P, diethylazodicarboxylate / tetrahydrofuran / Ambient temperature 2: 1.) aq. HCl, 2.) aq. NaHCO3 / 1) CH3OH, room temperature, 1.5 h; 2) room temperature, 16 h View Scheme
Multi-step reaction with 2 steps 1: 1) SOCl2 / 1) CHCl3, 45 deg C, 5 h, 2) CHCl3, reflux, 48 h 2: 80 percent / 1N HCl / methanol / 2 h / Heating View Scheme

methanol (67-56-1) + S-Ethyl (2R,3S)-3-benzoylamino-2-hydroxy-3-phenylpropanethioate (222727-06-2) → methyl (2R,3S)-3-benzoylamino-2-hydroxy-3-phenylpropanoate (32981-85-4)

Conditions	Yield
With silver trifluoroacetate Ambient temperature;	84%
With silver trifluoroacetate at 20℃; for 1h; Methylation;	84%

taxol (33069-62-4) → 10-deacetylbaccatin III (32981-86-5) + methyl (2R,3S)-3-benzoylamino-2-hydroxy-3-phenylpropanoate (32981-85-4) + 10-deacetyl-7-epi-baccatin III (71629-92-0)

Conditions	Yield
With lithium iodide In methanol for 10h; Ambient temperature;	A 58% B 82% C 40%
With lithium iodide In methanol for 10h; Ambient temperature;	A 58% B 82% C 40%

7-epipaclitaxel (105454-04-4) → 7-epi-baccatin III (31077-81-3) + methyl (2R,3S)-3-benzoylamino-2-hydroxy-3-phenylpropanoate (32981-85-4) + 10-deacetyl-7-epi-baccatin III (71629-92-0)

Conditions	Yield
With lithium iodide In methanol for 14h; Ambient temperature;	A 56% B 78% C 17%

(2aR,4S,4aS,6R,9S,11S,12S,12bS)-6,12b-bis(acetyloxy)-9-({(2R,3S)-3-(benzoylamino)-3-phenyl-2-[(triethylsilyl)oxy]propanoyl}oxy)-4,11-dihydroxy-4a,8,13,13-tetramethyl-5-oxo-2a,3,4,4a,5,6,9, 10,11,12,12a,12bdodecahydro-1H-7,11-methanocyclodeca[3,4]benzo[1,2-b]oxet-12-yl benzoate (148930-54-5) → 10-deacetylbaccatin III (32981-86-5) + methyl (2R,3S)-3-benzoylamino-2-hydroxy-3-phenylpropanoate (32981-85-4) + 10-deacetyl-7-epi-baccatin III (71629-92-0)

Conditions	Yield
With lithium iodide In methanol Ambient temperature; 2 weeks;	A 22% B 71% C 34%

methanol (67-56-1) + isobutyl (4S,5R)-3-benzoyl-4-phenyloxazolidin-2-one-5-carboxylate → methyl (2R,3S)-3-benzoylamino-2-hydroxy-3-phenylpropanoate (32981-85-4)

Conditions	Yield
With caesium carbonate In tetrahydrofuran at 20℃; for 1.5h;	51%

methanol (67-56-1) + 3-Benzoylamino-2-hydroxy-3-phenyl-propionic acid (1R,2R,3R,5S)-2,6,6-trimethyl-bicyclo[3.1.1]hept-3-yl ester → methyl (2R,3S)-3-benzoylamino-2-hydroxy-3-phenylpropanoate (32981-85-4) + methyl (2S,3R)-3-benzoylamino-2-hydroxy-3-phenylpropanoate (135821-94-2)

Conditions	Yield
In methanol Title compound not separated from byproducts;
With sodium methylate Title compound not separated from byproducts;

methanol (67-56-1) + 3-Benzoylamino-2-hydroxy-3-phenyl-propionic acid (1R,2S,5R)-2-isopropyl-5-methyl-cyclohexyl ester → methyl (2R,3S)-3-benzoylamino-2-hydroxy-3-phenylpropanoate (32981-85-4) + 3-Benzoylamino-2-hydroxy-3-phenyl-propionic acid methyl ester (503178-23-2) + methyl (2S,3R)-3-benzoylamino-2-hydroxy-3-phenylpropanoate (135821-94-2)

Conditions	Yield
In methanol Title compound not separated from byproducts;
With sodium methylate Title compound not separated from byproducts;

methanol (67-56-1) + 3-Benzoylamino-2-hydroxy-3-phenyl-propionic acid (1R,2S)-2-phenyl-cyclohexyl ester → methyl (2R,3S)-3-benzoylamino-2-hydroxy-3-phenylpropanoate (32981-85-4) + 3-Benzoylamino-2-hydroxy-3-phenyl-propionic acid methyl ester (503178-23-2) + methyl (2S,3R)-3-benzoylamino-2-hydroxy-3-phenylpropanoate (135821-94-2)

Conditions	Yield
In methanol Title compound not separated from byproducts;
With sodium methylate Title compound not separated from byproducts;

methanol (67-56-1) + 3-Benzoylamino-2-hydroxy-3-phenyl-propionic acid (1S,2R)-2-(1-methyl-1-phenyl-ethyl)-cyclohexyl ester → methyl (2R,3S)-3-benzoylamino-2-hydroxy-3-phenylpropanoate (32981-85-4) + 3-Benzoylamino-2-hydroxy-3-phenyl-propionic acid methyl ester (503178-23-2)

Conditions	Yield
In methanol Title compound not separated from byproducts;
With sodium methylate

methanol (67-56-1) + 3-Benzoylamino-2-hydroxy-3-phenyl-propionic acid (1R,2S,5R)-5-methyl-2-(1-methyl-1-phenyl-ethyl)-cyclohexyl ester → methyl (2R,3S)-3-benzoylamino-2-hydroxy-3-phenylpropanoate (32981-85-4) + 3-Benzoylamino-2-hydroxy-3-phenyl-propionic acid methyl ester (503178-23-2) + methyl (2S,3R)-3-benzoylamino-2-hydroxy-3-phenylpropanoate (135821-94-2)

Conditions	Yield
With sodium methylate Title compound not separated from byproducts;

sodium methylate (124-41-4) + (+)-cis-1-benzoyl-3-acetoxy-4-phenylazetidin-2-one → methyl (2R,3S)-3-benzoylamino-2-hydroxy-3-phenylpropanoate (32981-85-4)

Conditions	Yield
In methanol at 25℃; for 1h;	79 mg

benzoyl chloride (98-88-4) + (2R,3S)-3-phenylisoserine methyl ester (157240-36-3) → methyl (2R,3S)-3-benzoylamino-2-hydroxy-3-phenylpropanoate (32981-85-4)

Conditions	Yield
Yield given;
With sodium hydrogencarbonate In ethyl acetate
With sodium hydrogencarbonate In tetrahydrofuran; water at 0℃; for 2h;	0.123 g
With triethylamine
In dichloromethane at 20℃; for 5h; Time; Cooling with ice;	267 g

benzoyl chloride (98-88-4) + methyl (2R,3S)-2-hydroxy-3-phenyl-3-<(S)-1-methylbenzylamino>propanoate (147058-27-3) → methyl (2R,3S)-3-benzoylamino-2-hydroxy-3-phenylpropanoate (32981-85-4)

Conditions	Yield
With sodium hydroxide; hydrogen; palladium on activated charcoal 1.) MeOH, room temp., 30 h, 2.) THF, water, 0 deg C, 30 min; Yield given. Multistep reaction;

taxol → benzoic acid methyl ester (93-58-3) + methyl (2R,3S)-3-benzoylamino-2-hydroxy-3-phenylpropanoate (32981-85-4) + 7-epi-10-deacetyltaxol + 10-deacetyltaxol

Conditions	Yield
With hydrogenchloride In methanol Ambient temperature;

taxol → methyl (2R,3S)-3-benzoylamino-2-hydroxy-3-phenylpropanoate (32981-85-4)

Conditions	Yield
With ammonium hydroxide In methanol Ambient temperature;
With alkaline solution

(R)-3-benzamido-3-phenylpropanoic acid methyl ester (144494-74-6) → methyl (2R,3S)-3-benzoylamino-2-hydroxy-3-phenylpropanoate (32981-85-4) + methyl (2S,3S)-3-benzoylamino-2-hydroxy-3-phenylpropanoate (144541-45-7)

Conditions	Yield
With (+)-(2S,8aS)-(camphorylsulfonyl)oxaziridine; lithium chloride; lithium diisopropyl amide 1) -42 deg C, 2) -100 to -78 deg C; Yield given. Multistep reaction. Yields of byproduct given;
With MoO5*pyridine*HMPA; potassium hexamethylsilazane 1.) toluene, THF, -78 deg C to -25 deg C; 2.) toluene, THF, -60 deg C, 3 h; Yield given. Multistep reaction. Yields of byproduct given;

Benzoic acid (R)-2-azido-1-methoxycarbonyl-2-phenyl-ethyl ester → methyl (2R,3S)-3-benzoylamino-2-hydroxy-3-phenylpropanoate (32981-85-4) + (2R,3R)-(-)-2-hydroxy-3-(benzoylamino)-3-phenylpropanoic acid methyl ester (151764-53-3)

Conditions	Yield
With hydrogen; palladium on activated charcoal In methanol
With hydrogen; palladium on activated charcoal In methanol Title compound not separated from byproducts;

(2R,3S)-3-Benzoylamino-3-phenyl-2-trimethylsilanyloxy-propionic acid methyl ester (157722-43-5) → methyl (2R,3S)-3-benzoylamino-2-hydroxy-3-phenylpropanoate (32981-85-4)

Conditions	Yield
With potassium fluoride In water

syn-(+/-)-2-hydroxy-3-(benzoylamino)-3-phenylpropanoic acid methyl ester (32981-85-4, 132074-01-2, 135821-94-2, 144541-45-7) → methyl (2R,3S)-3-benzoylamino-2-hydroxy-3-phenylpropanoate (32981-85-4)

methanol (67-56-1) + taxol (33069-62-4) → methyl (2R,3S)-3-benzoylamino-2-hydroxy-3-phenylpropanoate (32981-85-4) + baccatin III (27548-93-2) + 7-epipaclitaxel (105454-04-4)

Conditions	Yield
at 58 - 116℃; Thermodynamic data; apparent activation energy Ea, other solvents, temperatures;

methyl (2R,3S)-3-benzoylamino-2-hydroxy-3-phenylpropanoate (32981-85-4) + (2-trimethylethylsilylethoxy)methyl chloride (76513-69-4) → (2R,3S)-N-benzoyl-O-<<2-(trimethylsilyl)ethoxy>methyl>-3-phenylisoserine methyl ester (99458-19-2)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In dichloromethane for 40h;	96%

methyl (2R,3S)-3-benzoylamino-2-hydroxy-3-phenylpropanoate (32981-85-4) + methanesulfonyl chloride (124-63-0) → (2R,3S)-3-benzoylamino-2-methanesulfonyloxy-3-phenylpropanoic acid methyl ester (274681-89-9)

Conditions	Yield
With triethylamine In tetrahydrofuran at 0 - 20℃;	93%
With triethylamine In tetrahydrofuran at 0 - 20℃; for 1.5h; Mesylation;	86%

p-Anisaldehyde dimethyl acetal (2186-92-7) + methyl (2R,3S)-3-benzoylamino-2-hydroxy-3-phenylpropanoate (32981-85-4) → Methyl (2R,4S,5R)-3-benzoyl-2-(p-methoxyphenyl)-4-phenyl-1,3-oxazolidine-5-carboxylate (157826-09-0)

Conditions	Yield
With pyridinium p-toluenesulfonate In cyclohexane; toluene	91%

1-methoxy-4-(methoxymethyl)benzene (1515-81-7) + methyl (2R,3S)-3-benzoylamino-2-hydroxy-3-phenylpropanoate (32981-85-4) → Methyl (2R,4S,5R)-3-benzoyl-2-(p-methoxyphenyl)-4-phenyl-1,3-oxazolidine-5-carboxylate (157826-09-0)

Conditions	Yield
With 2,3-dicyano-5,6-dichloro-p-benzoquinone In acetonitrile Heating;	90%
With 2,3-dicyano-5,6-dichloro-p-benzoquinone In acetonitrile at 60℃;	69%

2-Methoxypropene (116-11-0) + methyl (2R,3S)-3-benzoylamino-2-hydroxy-3-phenylpropanoate (32981-85-4) → Methyl (4S,5R)-3-benzoyl-2,2-dimethyl-4-phenyl-1,3-oxazolidine-5-carboxylate (202390-84-9)

Conditions	Yield
With pyridinium p-toluenesulfonate In toluene at 85℃;	89%
With pyridinium p-toluenesulfonate In toluene at 80℃; for 10h; Etherification; Cyclization;	89%
With toluene-4-sulfonic acid at 80℃;

methyl (2R,3S)-3-benzoylamino-2-hydroxy-3-phenylpropanoate (32981-85-4) → (4S,5S)-2,4-diphenyl-2-oxazoline-5-carboxylic acid methyl ester (227962-26-7)

Conditions	Yield
With dmap; trifluoromethylsulfonic anhydride In dichloromethane at -30℃; for 1h;	85%
With dmap; trifluoromethylsulfonic anhydride In dichloromethane at -30℃; for 1h; Cyclization; Dehydration;	84%
With dmap; sulfuryl dichloride In dichloromethane at 0℃; Cyclization;	65%
Multi-step reaction with 2 steps 1: 93 percent / Et3N / tetrahydrofuran / 0 - 20 °C 2: DBU / CHCl3 / 2 h / Heating View Scheme
Multi-step reaction with 2 steps 1: 86 percent / Et3N / tetrahydrofuran / 1.5 h / 0 - 20 °C 2: DBU / CHCl3 / 2 h / Heating View Scheme

methyl (2R,3S)-3-benzoylamino-2-hydroxy-3-phenylpropanoate (32981-85-4) + chloromethyl methyl ether (107-30-2) → (2R,3S)-N-benzoyl-O-(methoxymethyl)-3-phenylisoserine methyl ester (99458-17-0)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In dichloromethane for 40h;	82%

methyl (2R,3S)-3-benzoylamino-2-hydroxy-3-phenylpropanoate (32981-85-4) → (2R,3S)-N-benzoyl-3-phenylisoserine (132201-33-3)

Conditions	Yield
With potassium carbonate In methanol at 23℃; for 12h;	80%

p-Anisaldehyde dimethyl acetal (2186-92-7) + methyl (2R,3S)-3-benzoylamino-2-hydroxy-3-phenylpropanoate (32981-85-4) → Methyl (2S,4S,5R)-3-benzoyl-2-(p-methoxyphenyl)-4-phenyl-1,3-oxazolidine-5-carboxylate (202390-85-0)

Conditions	Yield
With camphor-10-sulfonic acid In toluene	79%

p-Anisaldehyde dimethyl acetal (2186-92-7) + methyl (2R,3S)-3-benzoylamino-2-hydroxy-3-phenylpropanoate (32981-85-4) → Methyl (2S,4S,5R)-3-benzoyl-2-(p-methoxyphenyl)-4-phenyl-1,3-oxazolidine-5-carboxylate (202390-85-0) + Methyl (2R,4S,5R)-3-benzoyl-2-(p-methoxyphenyl)-4-phenyl-1,3-oxazolidine-5-carboxylate (157826-09-0)

Conditions	Yield
With camphor-10-sulfonic acid In toluene at 130℃; Cycloaddition;	A 79% B 18%

Benzyloxymethyl chloride (3587-60-8) + methyl (2R,3S)-3-benzoylamino-2-hydroxy-3-phenylpropanoate (32981-85-4) → (2R,3S)-N-benzoyl-O-<(benzyloxy)methyl>-3-phenylisoserine methyl ester (99458-18-1)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In dichloromethane for 40h;	75%

methyl (2R,3S)-3-benzoylamino-2-hydroxy-3-phenylpropanoate (32981-85-4) + 1,4-dimethoxybezene (150-78-7) → Methyl (2R,4S,5R)-3-benzoyl-2-(p-methoxyphenyl)-4-phenyl-1,3-oxazolidine-5-carboxylate (157826-09-0)

Conditions	Yield
With 2,3-dicyano-5,6-dichloro-p-benzoquinone In acetonitrile at 70℃; for 0.116667h; Substitution; Cyclization;	75%

p-Anisaldehyde dimethyl acetal (2186-92-7) + methyl (2R,3S)-3-benzoylamino-2-hydroxy-3-phenylpropanoate (32981-85-4) → (4S,5R)-3-benzoyl-2-(4-methoxyphenyl)-4-phenyl-1,3-oxazolidine-5-carboxylic acid

Conditions	Yield
Stage #1: p-Anisaldehyde dimethyl acetal; methyl (2R,3S)-3-benzoylamino-2-hydroxy-3-phenylpropanoate With pyridinium p-toluenesulfonate In toluene for 6h; Inert atmosphere; Reflux; Stage #2: With methanol; sodium hydroxide In tetrahydrofuran at 0 - 25℃; for 3h;	75%

methyl (2R,3S)-3-benzoylamino-2-hydroxy-3-phenylpropanoate (32981-85-4) → (4S,5R)-2,4-diphenyl-2-oxazoline-5-carboxylic acid methyl ester (146848-91-1) + 3-N-benzoyl-4-phenyl-(4S,5R)-2-oxo-1,2,3-oxathiazolidine methyl ester (235432-33-4) + 3-N-benzoyl-4-phenyl-(4S,5R)-2-oxo-1,2,3-oxathiazolidine methyl ester (235432-34-5)

Conditions	Yield
With thionyl chloride; triethylamine In benzene at 0 - 5℃; for 0.25h; Cyclization;	A 3% B 68% C 14%

2,4-dimethoxybenzaldehyde dimethylacetal (91352-76-0) + methyl (2R,3S)-3-benzoylamino-2-hydroxy-3-phenylpropanoate (32981-85-4) → methyl-(4S,5R)-N-benzoyl-2-(2,4-dimethoxyphenyl)-4-phenyl-5-oxazolidine carboxylate + methyl-(4S,5R)-N-benzoyl-2-(2,4-dimethoxyphenyl)-4-phenyl-5-oxazolidine carboxylate

Conditions	Yield
With pyridinium p-toluenesulfonate In tetrahydrofuran at 100℃; for 1.5h; Condensation; Title compound not separated from byproducts;	A 64% B n/a

Upstream product

• 33069-62-4 taxol 
• 186581-53-3 diazomethane 
• 132201-33-3 (2R,3S)-N-benzoyl-3-phenylisoserine 
• 151671-04-4 methyl (4R,5S)-2,4-diphenyl-4,5-dihydro-1,3-oxazole-5-carboxylate 
• 51608-62-9 (E)-N-benzylidenebenzamide 
• 104196-23-8 (2S,3S)-2,3-epoxy-3-phenyl-1-propanol 
• 161513-45-7 tert-butyl (2S,3S,αS)-3--2-hydroxy-3-phenylpropionate 
• 153063-58-2 methyl (2R,3R)-2-benzyloxy-3-hydroxy-3-phenylpropanoate 
• 99458-15-8 Methyl (2R,3S)-(+)-2-hydroxy-3-azido-3-phenyl-propionate 
• 98-88-4 benzoyl chloride 
• 7440-05-3 palladium 
• 67-56-1 methanol 
• 132201-32-2 (2R,3S)-3-phenylisoserine hydrochloride 
• 131968-73-5 Chloro-acetic acid (3S,4R)-1-benzoyl-2-oxo-4-phenyl-azetidin-3-yl ester 

Downstream Products

• 99458-18-1 (2R,3S)-N-benzoyl-O-<(benzyloxy)methyl>-3-phenylisoserine methyl ester 
• 99458-19-2 (2R,3S)-N-benzoyl-O-<<2-(trimethylsilyl)ethoxy>methyl>-3-phenylisoserine methyl ester 
• 136561-53-0 (2R,3S)-2-hydroxy-3-amino-3-phenylpropionic acid 
• 202390-84-9 Methyl (4S,5R)-3-benzoyl-2,2-dimethyl-4-phenyl-1,3-oxazolidine-5-carboxylate 
• 274681-89-9 (2R,3S)-3-benzoylamino-2-methanesulfonyloxy-3-phenylpropanoic acid methyl ester 
• 153652-70-1 (4S,5R)-3-Benzoyl-2,2-dimethyl-4-phenyl-1,3-oxazolidine-5-carboxylic acid 
• 33069-62-4 taxol 
• 157826-10-3 (2R,4S,5R)-3-benzoyl-2-(4-methoxyphenyl)-4-phenyl-1,3-oxazolidine-5-carboxylic acid 
• 202390-86-1 (2S,4S,5R)-3-Benzoyl-2-(p-methoxyphenyl)-4-phenyl-1,3-oxazolidine-5-carboxylic acid 
• 157240-36-3 (2R,3S)-3-phenylisoserine methyl ester 
• 176298-46-7 2-hydroxy-3-(4-methyl benzenesulfonylamino)-3-phenyl-propionic acid methyl ester 
• 99458-22-7 (2R,3S)-N-benzoyl-O-<<2-(trimethylsilyl)ethoxy>methyl>-3-phenylisoserine 
• 99458-20-5 (2R,3S)-N-benzoyl-O-(methoxymethyl)-3-phenylisoserine 
• 99458-25-0 (2R,3S)-3-Benzoylamino-2-hydroxy-3-phenyl-propionic acid (1S,2S,3S,5R)-2,6,6-trimethyl-bicyclo[3.1.1]hept-3-yl ester 

Relevant articles and documents

Synthesis method of paclitaxel side chain and analogs thereof (by machine translation)

The invention discloses a synthesis method of a taxol side chain ((4S, 5R) -3 - benzoyl -2 - (4 - methoxyphenyl) -4 - phenyl -5 - oxazoline carboxylic acid) shown as a formula (f) and a series of reactions such as epoxidation, methyl esterification, ammonolysis, ester hydrolysis, condensation, configuration overturning, condensation and hydrolysis as well as analogues thereof. The invention discloses a synthesis method of the taxol side chain ((4S 5R) -3 -benzoyl -2 - (4 - methoxyphenyl) -4 - phenyl -5 - oxazoline carboxylic acid) and the like. The method has the advantages of short reaction time, high yield, good chiral selectivity, suitability for industrial production and the like. (by machine translation)

3-phenylisoserine derivative production method

The present invention provides a 3-phenylisoserine derivative production method for obtaining 3-phenylisoserine derivatives represented by formula (2) (in the formula, R1 represents a phenyl group or a phenyl group having a substituent group; R3 represents a hydrogen atom, a methyl group, a benzyl group, a p-methoxybenzyl group, a tert-butly group, a methoxymethyl group, a 2-tetrahydropyranyl group, an ethoxyethyl group, an acetyl group, a pivoloyl group, a benzoyl group, a trimethylsilyl group, a triethylsilyl group, or a tert-butyldimethylsilyl group; R4 represents a formyl group, an acetyl group, a benzoyl group, a tert-butoxycarbonyl group, or a benzyloxycarbonyl group; and R5 represents a C1-4 alkyl group) by protecting, in water or a mixed solvent containing water, the amino group of a compound represented by formula (1) (in the formula, R1 represents a phenyl group or a phenyl group having a substituent group; R2 represents an alkali metal, an alkaline earth metal, or a nitrogenous base; and R3 represents a hydrogen atom, a methly group, a benzyl group, a p-methoxybenzyl group, a tert-butyl group, a methoxymethyl group, a 2-tetrahydropyranyl group, an ethoxymethly group, an acetyl group, a pivoloyl group, a benzoyl group, a trimethylsilyl group, a triethylsilyl group, or a tert-butyldimethylsilyl group), and when a specific compound has been obtained, extracting the compound using a C4 ether solvent, and while removing the C4 ether solvent and moisture content, replacing at least some of the C4 ether solvent with a C1-4 aliphatic alcohol and implementing an esterification reaction, and then isolating the 3-phenylisoserine derivative at 0-30 DEG C. The 3-phenylisoserine derivative production method enables the production of 3-phenylisoserine derivatives having at least 99% purity.

Regio- and stereoselective methods for the conversion of (2S,3R)-β-phenylglycidic acid esters to taxoids and other enantiopure (2R,3S)-phenylisoserine esters

A novel efficient method was proposed for the synthesis of enantiopure precursors of taxane-containing cytostatics, i.e., methyl esters of (2R,3S)- and (2S,3R)-N-benzoylphenylisoserine and similar taxoid esters. The method is based on the regio- and stereoselective hydrobromolysis of the corresponding trans-β-phenyl glycidate enatiomers, consecutive reactions of O-acylcarbamoylation of the obtained 3-bromohydrins, intramolecular cyclization to 4-phenyloxazolidin-2-one-5-carboxylic acid derivatives, and oxazolidinone ring opening.