161596-47-0

Basic information

• Product Name: (S)-(+)-GLYCIDYL PHTHALIMIDE
• Synonyms: (S)-2-OXIRANYLMETHYL-ISOINDOLE-1,3-DIONE;(S)-(+)-GLYCIDYL PHTHALIMIDE;(S)-GLYCIDYL PHTHALIMIDE;2-[[(2S)-oxiran-2-yl]methyl]isoindole-1,3-dione;Rivaroxaban Impurity 39;2-((2S)-OXIRANYLMETHYL)-1H-ISOINDOLE-1,3(2H)-DIONE;(S)-(+)-N-(2,3-Epoxypropyl)phthalimide;(S)-N-Glycidylphthalimide
• CAS NO: 161596-47-0
• Molecular Formula: C₁₁H₉NO₃
• Molecular Weight: 203.19
• EINECS: 1308068-626-2
• Product Categories: N-Substituted Maleimides, Succinimides & Phthalimides;N-Substituted Phthalimides;Oxiranes;Simple 3-Membered Ring Compounds;Intermediate of Rivaroxaban
• Mol File: 161596-47-0.mol

Chemical Properties

• Melting Point: 102 °C
• Boiling Point: 347.4 °C at 760 mmHg
• Flash Point: 163.9 °C
• Appearance: /
• Density: 1.446 g/cm³
• Vapor Pressure: 5.38E-05mmHg at 25°C
• Refractive Index: 10 ° (C=2.2, CHCl3)
• Storage Temp.: under inert gas (nitrogen or Argon) at 2-8°C
• Solubility: Chloroform (Slightly), Ethyl Acetate (Slightly)
• PKA: -2.24±0.20(Predicted)
• CAS DataBase Reference: (S)-(+)-GLYCIDYL PHTHALIMIDE(CAS DataBase Reference)
• NIST Chemistry Reference: (S)-(+)-GLYCIDYL PHTHALIMIDE(161596-47-0)
• EPA Substance Registry System: (S)-(+)-GLYCIDYL PHTHALIMIDE(161596-47-0)

Safety Data

• Hazard Codes: Xi
• Statements: 41
• Safety Statements: 26-39
• WGK Germany: 2
• Hazardous Substances Data: 161596-47-0(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
(S)-(+)-GLYCIDYL PHTHALIMIDE is used as an intermediate for the production of the antibiotic Linezolid (L466500). Its unique chemical properties make it a crucial component in the synthesis process, contributing to the development of this important antibiotic.
Application Reason:
The use of (S)-(+)-GLYCIDYL PHTHALIMIDE in the pharmaceutical industry is primarily due to its ability to act as a key intermediate in the synthesis of Linezolid. This antibiotic is known for its effectiveness against a range of bacterial infections, including those caused by drug-resistant strains. By facilitating the production of Linezolid, (S)-(+)-GLYCIDYL PHTHALIMIDE plays a vital role in addressing the global need for effective antibiotics.

InChI:InChI=1/C11H9NO3/c13-10-8-3-1-2-4-9(8)11(14)12(10)5-7-6-15-7/h1-4,7H,5-6H2/t7-/m0/s1

Synthetic route

2-((S)-3-chloro-2-hydroxypropyl)isoindoline-1,3-dione (148857-42-5) → (S)-N-glycidylphthalimide (161596-47-0)

Conditions	Yield
With sodium carbonate In 5,5-dimethyl-1,3-cyclohexadiene for 4h; Reflux; Green chemistry;	94%
With sodium carbonate In 5,5-dimethyl-1,3-cyclohexadiene for 4h; Reflux;	89%
With potassium phosphate In 1,2-dichloro-ethane at 80℃; for 14h; Product distribution / selectivity;	n/a

1H-isoindole-1,3(2H)-dione, 2-[[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl] (40137-25-5) → (S)-N-glycidylphthalimide (161596-47-0)

Conditions	Yield
Stage #1: 1H-isoindole-1,3(2H)-dione, 2-[[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl] With hydrogen bromide In 1,2-dichloro-ethane at 10 - 15℃; for 4h; Stage #2: With sodium methylate In methanol at 0 - 15℃; for 3h;	93.6%
Multi-step reaction with 4 steps 1: hydrogenchloride / water / 2 h / 60 - 67 °C / Industrial scale 2: pyridinium p-toluenesulfonate / toluene / 0.25 h / 30 - 50 °C / Industrial scale 3: chloro-trimethyl-silane / toluene / 2.5 h / 30 °C 4: sodium methylate / methanol / 20 h / 30 °C View Scheme
Multi-step reaction with 4 steps 1: hydrogenchloride / water / 2 h / 60 - 67 °C / Industrial scale 2: pyridinium p-toluenesulfonate / toluene / 3 h / Dean-Stark; Reflux; Industrial scale 3: N-Bromosuccinimide / 1,2-dichloro-ethane / 1.33 h / 12 - 22 °C / Industrial scale 4: sodium methylate / toluene; methanol / 5.17 h / 9 - 22 °C / Industrial scale View Scheme

phthalimide (136918-14-4) + (S)-oxiranemethanol (60456-23-7) → (S)-N-glycidylphthalimide (161596-47-0)

Conditions	Yield
With triphenylphosphine; diethylazodicarboxylate In tetrahydrofuran at 0 - 20℃;	91%
With triphenylphosphine; diethylazodicarboxylate In tetrahydrofuran at 0 - 20℃;	91%
With triphenylphosphine; diethylazodicarboxylate In tetrahydrofuran at 20 - 25℃; for 18h;	80%

phthalimide (136918-14-4) + (R)-(-)-epichlorohydrin (51594-55-9) → (S)-N-glycidylphthalimide (161596-47-0)

Conditions	Yield
With benzyltrimethylammonium chloride In isopropyl alcohol at 40℃; for 22h;	90%
With potassium tert-butylate; benzyltrimethylammonium chloride; sodium carbonate In tetrahydrofuran at 50℃; for 39h;	81%
With benzyltrimethylammonium chloride; sodium hydrogencarbonate In isopropyl alcohol at 20℃; for 25h;	80%

C15H17NO4 → (S)-N-glycidylphthalimide (161596-47-0)

Conditions	Yield
Stage #1: C15H17NO4 With hydrogenchloride In dichloromethane; water at 10 - 15℃; for 4h; Stage #2: With sodium methylate In methanol at 0 - 15℃; for 3h; Reagent/catalyst;	89.7%

C17H21NO4 → (S)-N-glycidylphthalimide (161596-47-0)

Conditions	Yield
Stage #1: C17H21NO4 With hydrogen iodide In chloroform at 10 - 15℃; for 4h; Stage #2: With sodium ethanolate In ethanol at 0 - 15℃; for 3h;	85.9%

(R)-(-)-epichlorohydrin (51594-55-9) + potassium phtalimide (1074-82-4) → (S)-N-glycidylphthalimide (161596-47-0)

Conditions	Yield
With benzyltrimethylammonium chloride In isopropyl alcohol at 10℃; for 46h;	83%
With benzyltrimethylammonium chloride In tetrahydrofuran at 50℃; for 44h;	74%
With benzyltrimethylammonium chloride In methanol at 20℃; for 15h;	68%

phthalimide (136918-14-4) + (R)-(-)-epichlorohydrin (51594-55-9) → (S)-N-glycidylphthalimide (161596-47-0) + 2-((S)-3-chloro-2-hydroxypropyl)isoindoline-1,3-dione (148857-42-5)

Conditions	Yield
With potassium fluoride on basic alumina In 2-methyltetrahydrofuran for 3h; Inert atmosphere; Reflux; stereospecific reaction;	A 10% B 83%

(S)-epichlorohydrin (67843-74-7) + potassium phtalimide (1074-82-4) → (S)-N-glycidylphthalimide (161596-47-0)

Conditions	Yield
at 70℃; for 1h; Temperature;	83%
With N-benzyl-N,N,N-triethylammonium chloride; potassium iodide In isopropyl alcohol at 28℃; for 72h; Reagent/catalyst; Temperature; Solvent;	88.1 g

1H-isoindole-1,3(2H)-dione, 2-[2-(benzoyloxy)-3-bromopropyl] → (S)-N-glycidylphthalimide (161596-47-0)

Conditions	Yield
With sodium methylate In methanol; toluene at 9 - 22℃; for 5.16667h; Industrial scale;	80.8%

phthalimide (136918-14-4) + (S)-epichlorohydrin (67843-74-7) → (S)-N-glycidylphthalimide (161596-47-0)

Conditions	Yield
Stage #1: phthalimide; (S)-epichlorohydrin With methylamine In isopropyl alcohol at 60℃; for 5h; Stage #2: With sodium methylate In methanol; isopropyl alcohol at 10 - 30℃; Solvent; Reagent/catalyst;	77.5%
Stage #1: phthalimide; (S)-epichlorohydrin With N-benzyl-N,N,N-triethylammonium chloride; sodium carbonate In isopropyl alcohol at 20 - 40℃; Stage #2: With potassium tert-butylate In isopropyl alcohol at 5 - 10℃;
With sodium acetate In isopropyl alcohol at 65 - 70℃;	5 g
With 1-hexylamine hydrochloride; potassium tert-butylate; potassium iodide In isopropyl alcohol at 28℃; for 72h;	84.5 g

phthalimide (136918-14-4) + (R)-oxiranemethanol (57044-25-4) → (S)-N-glycidylphthalimide (161596-47-0)

Conditions	Yield
With triphenylphosphine; diethylazodicarboxylate In tetrahydrofuran at 20℃; for 4h;	53%

(R)-(-)-epichlorohydrin (51594-55-9) + potassium phtalimide (1074-82-4) → (-)-2-[(2R)-oxiran-2-ylmethyl]-1H-isoindole-1,3(2H)-dione (181140-34-1) + (S)-N-glycidylphthalimide (161596-47-0)

Conditions	Yield
With benzyltrimethylammonium chloride In DMF (N,N-dimethyl-formamide) at 20℃; for 16h;

2-(3-chloro-2-hydroxypropyl)-1H-isoindole-1,3(2H)-dione (19667-37-9, 34839-11-7, 148857-42-5, 148857-44-7) → (S)-N-glycidylphthalimide (161596-47-0)

Conditions	Yield
With potassium carbonate In toluene Reflux;	n/a
In tetrahydrofuran; water

(S)-2-(2-acetoxy-3-bromo-propyl)-isoindole-1,3-dione (879507-96-7) → (S)-N-glycidylphthalimide (161596-47-0)

Conditions	Yield
With potassium carbonate In methanol at 0℃; for 1h;

phthalimide (136918-14-4) + (R)-glycidyl tosylate (113826-06-5) → (S)-N-glycidylphthalimide (161596-47-0)

Conditions	Yield
With tetrabutylammomium bromide; potassium carbonate In acetone at 35 - 60℃; for 12h;
With tetrabutylammomium bromide; potassium carbonate In acetone at 25 - 60℃; for 12h;

phthalimide (136918-14-4) → (S)-N-glycidylphthalimide (161596-47-0)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: aluminum oxide / 1-methyl-pyrrolidin-2-one / 64 - 68 °C 1.2: 0.5 h 2.1: potassium carbonate / toluene / Reflux View Scheme
Multi-step reaction with 2 steps 1.1: aluminum oxide / 1-methyl-pyrrolidin-2-one / 64 - 68 °C 1.2: 0.5 h 2.1: potassium carbonate / toluene / Reflux View Scheme
Multi-step reaction with 2 steps 1.1: aluminum oxide / 1-methyl-pyrrolidin-2-one / 64 - 68 °C 1.2: 0.5 h 2.1: potassium carbonate / toluene / Reflux View Scheme

phthalimide (136918-14-4) + (S)-epichlorohydrin (67843-74-7) → 2-(3-chloro-2-hydroxypropyl)-1H-isoindole-1,3(2H)-dione (19667-37-9, 34839-11-7, 148857-42-5, 148857-44-7) + (S)-N-glycidylphthalimide (161596-47-0)

Conditions	Yield
With aluminum oxide In 1-methyl-pyrrolidin-2-one at 64 - 68℃;

potassium phtalimide (1074-82-4) → (S)-N-glycidylphthalimide (161596-47-0)

Conditions	Yield
Multi-step reaction with 4 steps 1: N-benzyl-N,N,N-triethylammonium chloride / N,N-dimethyl-formamide / 6 h / 100 - 120 °C / Industrial scale 2: pyridinium p-toluenesulfonate / toluene / 3 h / Dean-Stark; Reflux; Industrial scale 3: N-Bromosuccinimide / 1,2-dichloro-ethane / 1.33 h / 12 - 22 °C / Industrial scale 4: sodium methylate / toluene; methanol / 5.17 h / 9 - 22 °C / Industrial scale View Scheme
Multi-step reaction with 4 steps 1: N-benzyl-N,N,N-triethylammonium chloride / N,N-dimethyl-formamide / 6 h / 100 - 120 °C / Industrial scale 2: pyridinium p-toluenesulfonate / toluene / 0.25 h / 30 - 50 °C / Industrial scale 3: chloro-trimethyl-silane / toluene / 2.5 h / 30 °C 4: sodium methylate / methanol / 20 h / 30 °C View Scheme
Multi-step reaction with 2 steps 1.1: potassium iodide / N,N-dimethyl-formamide / 4 h / 80 - 85 °C 2.1: hydrogen bromide / 1,2-dichloro-ethane / 4 h / 10 - 15 °C 2.2: 3 h / 0 - 15 °C View Scheme

(S)-2-(2-methoxy-2-methyl-[1,3]dioxolane-4-ylmethyl)-isoindole-1,3-dione (879507-95-6) → (S)-N-glycidylphthalimide (161596-47-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: chloro-trimethyl-silane / toluene / 2.5 h / 30 °C 2: sodium methylate / methanol / 20 h / 30 °C View Scheme

(S)-2-phthalimido-1-(chloromethyl)ethyl acetate → (S)-N-glycidylphthalimide (161596-47-0)

Conditions	Yield
With sodium methylate In methanol at 30℃; for 20h;	65.6 kg

1H-isoindole-1,3(2H)-dione, 2-[[(4S)-2-phenyl-1,3-dioxolan-4-yl]methyl] → (S)-N-glycidylphthalimide (161596-47-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: N-Bromosuccinimide / 1,2-dichloro-ethane / 1.33 h / 12 - 22 °C / Industrial scale 2: sodium methylate / toluene; methanol / 5.17 h / 9 - 22 °C / Industrial scale View Scheme

1H-isoindole-1,3(2H)-dione, 2-[(2S)-2,3-dihydroxypropyl] (119835-88-0) → (S)-N-glycidylphthalimide (161596-47-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: pyridinium p-toluenesulfonate / toluene / 3 h / Dean-Stark; Reflux; Industrial scale 2: N-Bromosuccinimide / 1,2-dichloro-ethane / 1.33 h / 12 - 22 °C / Industrial scale 3: sodium methylate / toluene; methanol / 5.17 h / 9 - 22 °C / Industrial scale View Scheme
Multi-step reaction with 3 steps 1: pyridinium p-toluenesulfonate / toluene / 0.25 h / 30 - 50 °C / Industrial scale 2: chloro-trimethyl-silane / toluene / 2.5 h / 30 °C 3: sodium methylate / methanol / 20 h / 30 °C View Scheme

2-oxiranylmethylisoindole-1,3-dione (5455-98-1) → (-)-2-[(2R)-oxiran-2-ylmethyl]-1H-isoindole-1,3(2H)-dione (181140-34-1) + (S)-N-glycidylphthalimide (161596-47-0)

Conditions	Yield
With Cu metal organic framework based on (R)-3,3′-bis(6-carboxy-2-naphthyl)-2,2′-dihydroxy-1,1′-binaphthyl*silica packed stainless steel column (10 cm long × 4.0 mm i.d.) In ethanol; hexane at 25℃; Resolution of racemate;

2-((S)-3-bromo-2-hydroxypropyl)isoindoline-1,3-dione → (S)-N-glycidylphthalimide (161596-47-0)

Conditions	Yield
With sodium methylate In methanol; toluene at 5℃; for 0.75h;	34.1 g

2-((S)-3-p-toluenesulfonyloxy-2-hydroxypropyl)isoindoline-1,3-dione → (S)-N-glycidylphthalimide (161596-47-0)

Conditions	Yield
With sodium methylate In methanol; toluene at -5 - 20℃; for 1.25h;	35.8 g

N-(tert-butoxycarbonyl)-1,4-phenylenediamine (71026-66-9) + (S)-N-glycidylphthalimide (161596-47-0) → C22H25N3O5 (1082937-55-0)

Conditions	Yield
In isopropyl alcohol for 16h; Reflux;	100%
In isopropyl alcohol for 16h; Reflux;	100%
In isopropyl alcohol for 16h; Heating / reflux;	100%

N-benzyl-2,2-dimethoxyethylamine (54879-88-8) + (S)-N-glycidylphthalimide (161596-47-0) → (R)-2-{3-[benzyl-(2,2-dimethoxyethyl)amino]-2-hydroxypropyl}-1H-isoindole-1,3(2H)-dione (1374982-07-6)

Conditions	Yield
In ethanol for 20h; Inert atmosphere; Reflux;	100%

(S)-N-glycidylphthalimide (161596-47-0) → 2-((R)-3-Azido-2-hydroxy-propyl)-isoindole-1,3-dione

Conditions	Yield
With sodium azide; ammonium chloride In N,N-dimethyl-formamide at 80℃; for 1h;	100%
With sodium azide; ammonium chloride In N,N-dimethyl-formamide at 80℃;	100%

3-fluoro-4-(morpholin-4-yl)-phenyl isocyanate (224323-51-7) + (S)-N-glycidylphthalimide (161596-47-0) → 2-({(5S)-2-oxo-3-[(4-morpholino-3-fluorophenyl)]-4,5-dihydro-1,3-oxazole-5-yl}methyl)-isoindole-1,3-dione (168828-89-5)

Conditions	Yield
With lithium bromide at 120℃; for 4h; Temperature; Solvent;	96.51%
With lithium bromide In N,N-dimethyl-formamide at 60℃; for 4h; Reagent/catalyst; Solvent;	90.11%

4-(4-isocyanatophenyl)morpholin-3-one (1325210-64-7) + (S)-N-glycidylphthalimide (161596-47-0) → 2-({(5S)-2-oxo-3-[4-(3-oxo-4-morpholinyl)phenyl]-1,3-oxazolidin-5-yl}methyl)-1H-isoindole-1,3(2H)-dione (446292-08-6)

Conditions	Yield
With 3-methyl-1-butyl acetate; magnesium chloride at 120℃; for 4h; Solvent; Reagent/catalyst; Temperature;	95.5%
With lithium iodide In chlorobenzene at 115℃; for 4h; Reagent/catalyst; Solvent; Temperature;	94.09%

(S)-N-glycidylphthalimide (161596-47-0) + 4-(4-aminophenyl)morpholin-3-one (438056-69-0) → 2-((2R)-2-hydroxy-3-{[4-(3-oxo-4-morpholinyl)phenyl]amino}propyl)-1H-isoindole-1,3(2H)-dione (446292-07-5)

Conditions	Yield
In ethanol; water at 20℃; for 15h; Solvent; Temperature;	95%
In ethanol; water for 27h; Heating;	92%
In methanol; water at 65 - 70℃; for 32h;	92%

(S)-N-glycidylphthalimide (161596-47-0) + 4-(4-aminophenyl)morpholin-3-one (438056-69-0) → 2-((2R)-2-hydroxy-3-{[4-(3-oxomorpholin-4-yl)phenyl]amino}propyl)-1H-isoindole-1,3(2H)-dione

Conditions	Yield
In water; toluene at 30 - 85℃; Solvent; Temperature;	94.6%

3-fluoro-4-(morpholinyl)aniline (93246-53-8) + (S)-N-glycidylphthalimide (161596-47-0) → N-[3-phthalimido-2-(R)-hydroxypropyl]-3-fluoro-4-(4-morpholinyl)aniline (874340-08-6)

Conditions	Yield
In ethanol; water at 80℃; for 14h;	94.4%
In N,N-dimethyl-formamide for 5h; Product distribution / selectivity; Heating / reflux;
In N,N-dimethyl-formamide

N-acetyl-p-phenylenediamine (122-80-5) + (S)-N-glycidylphthalimide (161596-47-0) → C19H19N3O4

Conditions	Yield
In isopropyl alcohol for 16h; Reflux;	93.8%

(S)-N-glycidylphthalimide (161596-47-0) → 2-((S)-3-chloro-2-hydroxypropyl)isoindoline-1,3-dione (148857-42-5)

Conditions	Yield
Stage #1: (S)-N-glycidylphthalimide With Chloroiodomethane In 2-methyltetrahydrofuran at -78℃; for 0.0333333h; Stage #2: With methyllithium In 2-methyltetrahydrofuran; diethyl ether at -78℃; for 1h; Solvent; Reagent/catalyst; Temperature; enantioselective reaction;	93%
With C25H21OP; trichloroacetonitrile In water; N,N-dimethyl-formamide at 25℃; for 6h; Inert atmosphere; Irradiation;	78%

4-nitro-aniline (100-01-6) + (S)-N-glycidylphthalimide (161596-47-0) → C17H15N3O5

Conditions	Yield
In ethanol at 50℃; Solvent; Temperature;	91%

(S)-N-glycidylphthalimide (161596-47-0) → C11H10INO3

Conditions	Yield
Stage #1: (S)-N-glycidylphthalimide With diiodomethane In 2-methyltetrahydrofuran at -78℃; for 0.0333333h; Stage #2: With methyllithium In 2-methyltetrahydrofuran; diethyl ether at -78℃; for 1h; enantioselective reaction;	91%

3-fluoro-4-(morpholinyl)aniline (93246-53-8) + (S)-N-glycidylphthalimide (161596-47-0) → C21H22FN3O4

Conditions	Yield
In ethanol at 60℃; for 16h; Temperature; Inert atmosphere;	90.09%

(S)-N-glycidylphthalimide (161596-47-0) → 2-((S)-3-bromo-2-hydroxypropyl)isoindoline-1,3-dione

Conditions	Yield
Stage #1: (S)-N-glycidylphthalimide With iodobromomethane In 2-methyltetrahydrofuran at -78℃; for 0.0333333h; Stage #2: With methyllithium In 2-methyltetrahydrofuran; diethyl ether at -78℃; for 1h; enantioselective reaction;	89%

C10H8(2)H4N2O2 + (S)-N-glycidylphthalimide (161596-47-0) → C21H17(2)H4N3O5

Conditions	Yield
In ethanol; water at 0℃; for 32h; Reflux;	88%

2-hydroxy-2-methylpropanenitrile (75-86-5) + (S)-N-glycidylphthalimide (161596-47-0) → (S)-4-(1,3-dioxoisoindol-2-yl)-3-hydroxybutyronitrile (929281-94-7)

Conditions	Yield
With triethylamine In tetrahydrofuran at 75℃;	87%

phenyl isocyanate (103-71-9) + (S)-N-glycidylphthalimide (161596-47-0) → (S)-2-((2-oxo-3-phenyloxazolidin-5-yl)methyl)isoindoline-1,3-dione

Conditions	Yield
With (2-hydroxy-5-methylphenyl)triphenylphosphonium iodide In chlorobenzene at 100℃; for 6h; Inert atmosphere;	87%

methyl (3-fluoro-4-morpholinophenyl)carbamate (212325-40-1) + (S)-N-glycidylphthalimide (161596-47-0) → 2-({(5S)-2-oxo-3-[(4-morpholino-3-fluorophenyl)]-4,5-dihydro-1,3-oxazole-5-yl}methyl)-isoindole-1,3-dione (168828-89-5)

Conditions	Yield
With lithium tert-butoxide In N,N-dimethyl-formamide at 25 - 85℃; Temperature; Solvent; Reagent/catalyst;	85%
With lithium tert-butoxide In ethyl acetate at 25 - 75℃; Solvent; Temperature; Reagent/catalyst;	70%

(S)-N-glycidylphthalimide (161596-47-0) + p-aminoiodobenzene (540-37-4) → (R)-2-(2-hydroxy-3-((4-iodophenyl)amino)propyl)isoindolin-1,3-one

Conditions	Yield
In ethanol; water at 100℃; for 12h;	84.9%

C24H26N2O3 + (S)-N-glycidylphthalimide (161596-47-0) → C35H35N3O6

Conditions	Yield
In methanol; ethanol at 75℃; for 48h; Temperature; Solvent;	84.7%

(S)-N-glycidylphthalimide (161596-47-0) + 4-Aminobenzonitrile (873-74-5) → 4-(3-(1,3-dioxoisoindolin-2-yl)-2-hydroxypropylamino)benzonitrile (1261131-68-3)

Conditions	Yield
at 105℃; for 13h;	84%
With magnesium(II) perchlorate In 1,4-dioxane for 10h; Reflux;	78%

(S)-N-glycidylphthalimide (161596-47-0) + dibenzylamine (103-49-1) → 2-[(2R)-3-(dibenzylamino)-2-hydroxy-propyl]isoindoline-1,3-dione (1357474-57-7)

Conditions	Yield
In isopropyl alcohol at 0℃; for 9h; Reflux; Inert atmosphere; regioselective reaction;	84%

benzyl 3-fluoro-4-(4-morpholinyl)phenylcarbamate (168828-81-7, 1027135-00-7) + (S)-N-glycidylphthalimide (161596-47-0) → 2-({(5S)-2-oxo-3-[(4-morpholino-3-fluorophenyl)]-4,5-dihydro-1,3-oxazole-5-yl}methyl)-isoindole-1,3-dione (168828-89-5)

Conditions	Yield
Stage #1: benzyl 3-fluoro-4-(4-morpholinyl)phenylcarbamate With lithium tert-butoxide In tetrahydrofuran; N,N-dimethyl-formamide at 5℃; for 0.5h; Inert atmosphere; Stage #2: (S)-N-glycidylphthalimide In tetrahydrofuran; N,N-dimethyl-formamide at 5 - 20℃; for 24h; Reagent/catalyst; Temperature; Inert atmosphere;	84%

7-fluoro-1-(piperazin-1-yl)isoquinoline + (S)-N-glycidylphthalimide (161596-47-0) → 2-[(2R)-3-[4-(7-fluoroisoquinolin-1-yl)piperazin-1-yl]-2-hydroxypropyl]-2,3-dihydro-1H-isoindole-1,3-dione

Conditions	Yield
In acetonitrile at 70℃; for 6h;	84%

Upstream product

• 148857-42-5 2-((S)-3-chloro-2-hydroxypropyl)isoindoline-1,3-dione 
• 51594-55-9 (R)-(-)-epichlorohydrin 
• 1074-82-4 potassium phtalimide 
• 136918-14-4 phthalimide 
• 57044-25-4 (R)-oxiranemethanol 
• 113826-06-5 (R)-glycidyl tosylate 
• 5455-98-1 2-oxiranylmethylisoindole-1,3-dione 
• 119835-88-0 1H-isoindole-1,3(2H)-dione, 2-[(2S)-2,3-dihydroxypropyl] 
• 879507-95-6 (S)-2-(2-methoxy-2-methyl-[1,3]dioxolane-4-ylmethyl)-isoindole-1,3-dione 
• 40137-25-5 1H-isoindole-1,3(2H)-dione, 2-[[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl] 
• 67843-74-7 (S)-epichlorohydrin 
• 879507-96-7 (S)-2-(2-acetoxy-3-bromo-propyl)-isoindole-1,3-dione 
• 19667-37-9 2-(3-chloro-2-hydroxypropyl)-1H-isoindole-1,3(2H)-dione 
• 60456-23-7 (S)-oxiranemethanol 

Downstream Products

• 610785-35-8 2-{(2R)-3-[(3,4-dichlorobenzyl)(2-hydroxyethyl)amino]-2-hydroxypropyl}-1H-isoindole-1,3(2H)-dione 
• 446292-07-5 2-((2S)-2-hydroxy-3-{[4-(3-oxomorpholin-4-yl)phenyl]amino}propyl)-1H-isoindole-1,3(2H)-dione 
• 446292-08-6 2-({(5S)-2-oxo-3-[4-(3-oxo-4-morpholinyl)phenyl]-1,3-oxazolidin-5-yl}methyl)-1H-isoindole-1,3(2H)-dione 
• 1261131-70-7 (S)-4-(5-((1,3-dioxoisoindolin-2-yl)methyl)-2-oxooxazolidin-3-yl)benzonitrile 
• 165800-03-3 linezolid 
• 366789-02-8 Rivaroxaban 
• 1643354-27-1 2,2'-((2R,2'R)-((4-(3-oxomorpholino)phenyl)azadiyl)bis(2-hydroxypropane-3,1-diyl))bis(isoindoline-1,3-dione) 
• 168828-89-5 2-({(5S)-2-oxo-3-[(4-morpholino-3-fluorophenyl)]-4,5-dihydro-1,3-oxazole-5-yl}methyl)-isoindole-1,3-dione 
• 1374982-08-7 (2R,6S)-2-[(4-benzyl-6-methoxymorpholin-2-yl)methyl]-1H-isoindole-1,3(2H)-dione 
• 1374982-09-8 (2R,6R)-2-[(4-benzyl-6-methoxymorpholin-2-yl)methyl]-1H-isoindole-1,3(2H)-dione 
• 1374982-07-6 (R)-2-{3-[benzyl-(2,2-dimethoxyethyl)amino]-2-hydroxypropyl}-1H-isoindole-1,3(2H)-dione 
• 1309774-73-9 2-[(2R)-2-hydroxy-3-[[(1R)-2-hydroxy-1-phenyl-ethyl]amino]propyl] isoindoline-1,3-dione 
• 1309774-76-2 2-[(2R)-2-hydroxy-3-[[(1S)-1-phenylethyl]amino]propyl]isoindoline-1,3-dione 
• 1330779-60-6 C₂₁H₂₁Cl₂N₃O₃ 

Relevant articles and documents

Novel series of highly potent non-peptide growth hormone secretagogues with improved bioavailability

The discovery and the SAR of acylproline derivatives as highly potent growth hormone secretagogues (GHSs) with good oral bioavailability are described. One representative compound, N-[3-(2,2-dimethylpropylamino)-2-hydroxypropyl]-2(R)-[1-(2,2-dimethylpropionyl)pyrrolidine-2(S)- carbonylamino]-3-naphthalen-2-ylpropionamide (4e), showed potent GHS activity (ED50=1 nM) and good oral bioavailability (BA=33.2%). Moreover, the optically pure N-[3-(2,2-dimethylpropylamino)-2(S)-hydroypropyl]-2(R)-[1-(2,2-dimethylpropionyl)pyrrolidine-2(S)-carbonylamino]-3-naphthalen-2- ylpropionamide ((2S)-4e) showed a good metabolic stability against in vitro clearance (human liver microsome) with potent GHS activity.

Preparation method of (S)-glycidyl phthalimide

The invention provides a preparation method of (S)-glycidyl phthalimide (II). Phthalimide (III) and (S)-1-substituted epoxypropane (IV) which are used as raw materials react under the action of a catalyst to generate 2-((S)-3-substituted-2-hydroxypropyl)isoindoline-1,3-dione (V), and the 2-((S)-3-substituted-2-hydroxypropyl)isoindoline-1,3-dione (V) is subjected to a cyclization reaction to obtainthe (S)-glycidyl phthalimide (II). The method has the advantages of cheap and easily available raw materials, easiness in realization of reaction conditions, low cost, short reaction route, simplicity in operation, simplicity in post-treatment, few side reactions, high yield and high purity of the target product, and suitableness for industrial production.

Preparation method of rivaroxaban intermediate

The invention provides a preparation method of a rivaroxaban intermediate. The preparation method comprises: (1) carrying out a reaction on a compound A and a compound B in an alcohol or an alcohol aqueous solution to obtain a compound C; and (2) reacting the compound C with N,N'-carbonyldiimidazole in a reaction solvent selected from acetonitrile or butyronitrile to obtain a reaction solution containing a compound D, and performing cooling crystallization to obtain a compound D.

Low-cost and high-purity S-glycidyl phthalimide synthesis method

The invention relates to a low-cost and high-purity S-glycidyl phthalimide synthesis method, which comprises: carrying out a substitution reaction on potassium phthalimide and R-2,2-disubstituted-4-halomethyl-1,3-dioxolane to generate N-(S-2,2-disubstituted-1,3-dioxolane-4-)methylphthalimide, carrying out a ketone (aldehyde) removing ring-opening reaction to produce N-2-S-hydroxy-3-halogenated n-propyl phthalimide, and finally carrying out an elimination reaction to remove hydrogen halide so as to generate S-glycidyl phthalimide, wherein S-glycidyl phthalimide is the key intermediate for the preparation of rivaroxaban. According to the present invention, the synthesis method has advantages of inexpensive and easily-available raw materials, high stability, high reaction selectivity and highproduction efficiency, and the obtained S-glycidyl phthalimide has advantages of low cost and high purity, and is favorable for the industrial production of high-purity rivaroxaban.

A novel homochiral metal-organic framework with an expanded open cage based on (: R)-3,3′-bis(6-carboxy-2-naphthyl)-2,2′-dihydroxy-1,1′-binaphthyl: synthesis, X-ray structure and efficient HPLC enantiomer separation

A new homochiral metal-organic framework (MOF) with an expanded open cage based on the (R)-3,3′-bis(6-carboxy-2-naphthyl)-2,2′-dihydroxy-1,1′-binaphthyl ligand was synthesized and utilized as a novel chiral stationary phase for high-performance liquid chromatography. Twelve racemates including sec-alcohols, sulfoxides, epoxides, lactone, 1,3-dioxolan-2-one, and oxazolidinone were used as analytes for evaluating the separation properties of the chiral-MOF-packed column. Experimentally, the homochiral MOF offered good molecular recognition ability, which suggests good prospects for the application of chiral MOFs as stationary phases for enantioseparation.

Preparation method of S-N-glycidol phthalimide

The invention relates to a preparation method of S-N-glycidol phthalimide. According to the method, recyclable anion exchange resin is used for catalyzing reaction in the preparation process of the S-N-glycidol phthalimide, so that the production cost is reduced; the emission requirements are reduced; the problem that a phase transfer catalyst is difficultly removed and influences the quality of aproduct is solved; the reaction time is further reduced; the special requirements on equipment caused by application of potassium tert-butoxide are avoided; the production cost is reduced; the preparation method is suitable for industrial production.

Preparation method of rivaroxaban intermediate

The invention relates to a preparation method of rivaroxaban intermediate S-N-glycidyl phthalimide. According to the method, catalytic reaction is carried out by using recoverable aluminum oxide in apreparation process of S-N-glycidyl phthalimide, so that the production cost is reduced, the emission requirement is reduced, the problem that the product quality is affected by a phase transfer catalyst difficultly eliminated is solved, the reaction time is further shortened, the special requirement on equipment caused by the use of potassium tert-butanolate is avoided, the production cost is reduced, and therefore, the preparation method is particularly suitable for industrial production.

Process for the preparation of linezolid

The present invention relates to an improved process for the preparation of Linezolid. More specifically, the present invention relates to an improved process for preparing (S)—N-[[3-[3-fluoro-4-[4-morpholinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl] phthalimide and (S)-glycidyl phthalimide intermediates, which are used in the preparation of Linezolid.

Pilot scale process development of SL65.0102-10, an N-diazabicyclo[2.2.2]-octylmethyl Benzamide

The process development and improvements for route selection, adapted to large scale for the pilot-scale preparation of SL65.0102-10, an N-diazabicyclo[2.2.2]-octylmethyl benzamide, a 5-HT3 and 5-HT4 receptor active ligand for the treatment of neurological disorders such as cognition impairment, are described in this article. Notable steps and enhancements are compared to the original route, including the improvement of a chiral epoxide synthesis by shortening the number of chemical steps, the deprotection of a quaternary ammonium salt, and the redesign of the final amidification coupling to avoid chromatography.

AN IMPROVED PROCESS FOR THE PREPARATION OF LINEZOLID

The present invention relates to an improved process for the preparation of Linezolid. More specifically, the present invention relates to an improved process for preparing(S)-N-[[3-[3-fluoro-4-[4-morpholinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl] phthalimide and (S)-glycidyl phthalimide intermediates, which are used in the preparation of Linezolid.