118289-55-7

Basic information

• Product Name: 5-Chloroethyl-6-chloro-1,3-dihydro-2H-indole-2-one
• Synonyms: 2H-INDOLE-2-ONE,5-CHLOROETHYL-6-CHLORO-1,3-DIHYDRO;5-CHLOROETHYL-6-CHLORO-1,3-DIHYDRO-1H-INDOL-2-ONE;5-CHLOROETHYL-6-CHLORO-1,3-DIHYDRO-2H-INDOLE-2-ONE;6-CHLORO-5-(2-CHLOROETHYL)-1,3-DIHYDRO-2H-INDOL-2-ONE;5-(2-CHLOROETHYL)-1,3-DIHYDRO-2H-6-CHLOROINDULE-2-ONE;2H-Indol-2-one-6-chloro-5-(2-chloroethyl)-1,3-dihydro;5-Chloroethyl-6-chloro-1,3-dihydro-2H-indol-2-one;6-Chloro-5-(2-Chloroethyl)-1,3
• CAS NO: 118289-55-7
• Molecular Formula: C₁₀H₉Cl₂NO
• Molecular Weight: 230.09
• EINECS: 421-320-0
• Product Categories: Indole;Indoles;(intermediate of ziprasidone hcl);Intermediates of Ziprasidone;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 118289-55-7.mol
• Article Data: 14

Chemical Properties

• Melting Point: 218-221℃
• Boiling Point: 393.82 °C at 760 mmHg
• Flash Point: 191.976 °C
• Appearance: /
• Density: 1.376 g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.592
• Storage Temp.: Refrigerator
• Solubility: soluble in Dimethylformamide
• PKA: 13.23±0.20(Predicted)
• CAS DataBase Reference: 5-Chloroethyl-6-chloro-1,3-dihydro-2H-indole-2-one(CAS DataBase Reference)
• NIST Chemistry Reference: 5-Chloroethyl-6-chloro-1,3-dihydro-2H-indole-2-one(118289-55-7)
• EPA Substance Registry System: 5-Chloroethyl-6-chloro-1,3-dihydro-2H-indole-2-one(118289-55-7)

Safety Data

• Hazard Codes: N
• Statements: 50/53
• Safety Statements: 60-61-24/25
• RIDADR: 3077
• HazardClass: 9
• PackingGroup: III
• Hazardous Substances Data: 118289-55-7(Hazardous Substances Data)

Usage

Chemical Properties

Pale Pink Solid

Uses

6-Chloro-5-(2-chloroethyl)oxindole (cas# 118289-55-7) is a compound useful in organic synthesis.

InChI:InChI=1/C10H9Cl2NO/c11-2-1-6-3-7-4-10(14)13-9(7)5-8(6)12/h3,5H,1-2,4H2,(H,13,14)

Synthetic route

6-chloro-5-(2-hydroxyethyl)-2-oxindole → 6-chloro-5-(2-chloroethyl)-2-oxindole (118289-55-7)

Conditions	Yield
With triphenylphosphine In tetrahydrofuran; tetrachloromethane for 3h; Reflux;	97%

C17H16ClNO4S → 6-chloro-5-(2-chloroethyl)-2-oxindole (118289-55-7)

Conditions	Yield
With lithium chloride In N,N-dimethyl-formamide at 50℃; for 8h;	95%

6-chloro-5-(2-chloroacetyl) indolin-2-one (118307-04-3) → 6-chloro-5-(2-chloroethyl)-2-oxindole (118289-55-7)

Conditions	Yield
With triethylsilane; trifluoroacetic acid
Stage #1: 6-chloro-5-(2-chloroacetyl) indolin-2-one With triethylsilane; trifluoroacetic acid at 0 - 35℃; for 7h; Stage #2: With water at 5 - 10℃; for 1h;
With triethylsilane In trifluoroacetic acid at -5 - 45℃; for 7.5h;

6-chloro-2-oxindole (56341-37-8) → 6-chloro-5-(2-chloroethyl)-2-oxindole (118289-55-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: AlCl3 / CS2 2: Et3SiH, CF3COOH View Scheme
Multi-step reaction with 2 steps 1.1: aluminum (III) chloride / 1,2-dichloro-ethane / 20 °C / Inert atmosphere 1.2: 35 - 37 °C / Inert atmosphere 2.1: trifluoroacetic acid / 0.25 h / 25 - 30 °C / Inert atmosphere 2.2: 0 - 35 °C / Inert atmosphere View Scheme
Multi-step reaction with 2 steps 1: aluminum (III) chloride / dichloromethane / 20 h / Reflux; Inert atmosphere 2: aluminum (III) chloride; 1,1,3,3-Tetramethyldisiloxane / dichloromethane / 0 °C / Inert atmosphere View Scheme

6-chloro-5-(2-chloroacetyl) indolin-2-one (118307-04-3) → 6-chloro-5-(2-chloro-1-hydroxyethyl) indolin-2-one (884305-06-0) + 6-chloro-5-(2-chloroethyl)-2-oxindole (118289-55-7)

Conditions	Yield
With triethylsilane; trifluoroacetic acid for 7h;
With aluminum (III) chloride; 1,1,3,3-Tetramethyldisiloxane In dichloromethane at 0℃; Inert atmosphere; chemoselective reaction;

6-chloro-5-(2-chloro-1-hydroxyethyl) indolin-2-one (884305-06-0) → 6-chloro-5-(2-chloroethyl)-2-oxindole (118289-55-7)

Conditions	Yield
Stage #1: 6-chloro-5-(2-chloro-1-hydroxyethyl) indolin-2-one With trifluoroacetic acid at 20℃; for 1h; Stage #2: With triethylsilane at 35 - 40℃; for 13.5 - 15.5h;
Stage #1: 6-chloro-5-(2-chloro-1-hydroxyethyl) indolin-2-one With trifluoroacetic acid at 20℃; for 1h; Stage #2: With triethylsilane at 35 - 40℃; for 13.5 - 15.5h;

2,5-dichloronitrobenzene (89-61-2) → 6-chloro-5-(2-chloroethyl)-2-oxindole (118289-55-7)

Conditions

Yield

Multi-step reaction with 4 steps 1.1: potassium carbonate / dimethyl sulfoxide / 25 - 30 °C / Inert atmosphere 1.2: 16 h / 40 - 85 °C 2.1: hydrogenchloride; tin / water; methanol / 10 - 70 °C 3.1: aluminum (III) chloride / 1,2-dichloro-ethane / 20 °C / Inert atmosphere 3.2: 35 - 37 °C / Inert atmosphere 4.1: trifluoroacetic acid / 0.25 h / 25 - 30 °C / Inert atmosphere 4.2: 0 - 35 °C / Inert atmosphere View Scheme

dimethyl (4-chloro-2-nitrophenyl)malonate (147124-32-1) → 6-chloro-5-(2-chloroethyl)-2-oxindole (118289-55-7)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: hydrogenchloride; tin / water; methanol / 10 - 70 °C 2.1: aluminum (III) chloride / 1,2-dichloro-ethane / 20 °C / Inert atmosphere 2.2: 35 - 37 °C / Inert atmosphere 3.1: trifluoroacetic acid / 0.25 h / 25 - 30 °C / Inert atmosphere 3.2: 0 - 35 °C / Inert atmosphere View Scheme

6-chloro-5-(2-chloroacetyl) indolin-2-one (118307-04-3) → 6-chloro-5-(2-chloro-1-hydroxyethyl) indolin-2-one (884305-06-0) + 6-chloro-5-ethylindolin-2-one + 6-chloro-5-(2-chloroethyl)-2-oxindole (118289-55-7)

Conditions	Yield
With triethylsilane; aluminum (III) chloride In dichloromethane at 0 - 20℃; for 12h; Inert atmosphere; Reflux;

6-chloro-5-(2-chloroacetyl) indolin-2-one (118307-04-3) → 6-chloro-5-ethylindolin-2-one + 6-chloro-5-(2-chloroethyl)-2-oxindole (118289-55-7)

Conditions	Yield
With aluminum (III) chloride; dimethylmonochlorosilane In dichloromethane at 0℃; Inert atmosphere; chemoselective reaction;

6-chloro-2-oxindole (56341-37-8) → 6-chloro-5-(2-chloro-1-hydroxyethyl) indolin-2-one (884305-06-0) + 6-chloro-5-ethylindolin-2-one + 6-chloro-5-(2-chloroethyl)-2-oxindole (118289-55-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: aluminum (III) chloride / dichloromethane / 20 h / Reflux; Inert atmosphere 2: aluminum (III) chloride; triethylsilane / dichloromethane / 12 h / 0 - 20 °C / Inert atmosphere; Reflux View Scheme

6-chloro-2-oxindole (56341-37-8) → 6-chloro-5-(2-chloro-1-hydroxyethyl) indolin-2-one (884305-06-0) + 6-chloro-5-(2-chloroethyl)-2-oxindole (118289-55-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: aluminum (III) chloride / dichloromethane / 20 h / Reflux; Inert atmosphere 2: aluminum (III) chloride; 1,1,3,3-Tetramethyldisiloxane / dichloromethane / 0 °C / Inert atmosphere View Scheme

5-chloro-2,4-difluoronitrobenzene (1481-68-1) → 6-chloro-5-(2-chloroethyl)-2-oxindole (118289-55-7)

Conditions	Yield
Multi-step reaction with 6 steps 1: N,N-dimethyl-formamide / 12 h / 100 °C 2: hydrogenchloride; acetic acid / water / 18 h / Reflux 3: thionyl chloride / 4 h / 20 °C 4: acetic acid; hydrogen / 3 h / 20 °C / 2327.23 Torr 5: sodium tetrahydroborate; lithium bromide; Trimethyl borate / tetrahydrofuran / 18 h / Reflux 6: triphenylphosphine / tetrahydrofuran; tetrachloromethane / 3 h / Reflux View Scheme
Multi-step reaction with 7 steps 1: N,N-dimethyl-formamide / 12 h / 100 °C 2: hydrogenchloride; acetic acid / water / 18 h / Reflux 3: thionyl chloride / 4 h / 20 °C 4: acetic acid; hydrogen / 3 h / 20 °C / 2327.23 Torr 5: sodium tetrahydroborate; lithium bromide; Trimethyl borate / tetrahydrofuran / 18 h / Reflux 6: triethylamine; dmap / dichloromethane / 5 h / Reflux 7: lithium chloride / N,N-dimethyl-formamide / 8 h / 50 °C View Scheme

tetraethyl 4-chloro-6-nitro-1,3-benzenedimalonate → 6-chloro-5-(2-chloroethyl)-2-oxindole (118289-55-7)

Conditions	Yield
Multi-step reaction with 5 steps 1: hydrogenchloride; acetic acid / water / 18 h / Reflux 2: thionyl chloride / 4 h / 20 °C 3: acetic acid; hydrogen / 3 h / 20 °C / 2327.23 Torr 4: sodium tetrahydroborate; lithium bromide; Trimethyl borate / tetrahydrofuran / 18 h / Reflux 5: triphenylphosphine / tetrahydrofuran; tetrachloromethane / 3 h / Reflux View Scheme
Multi-step reaction with 6 steps 1: hydrogenchloride; acetic acid / water / 18 h / Reflux 2: thionyl chloride / 4 h / 20 °C 3: acetic acid; hydrogen / 3 h / 20 °C / 2327.23 Torr 4: sodium tetrahydroborate; lithium bromide; Trimethyl borate / tetrahydrofuran / 18 h / Reflux 5: triethylamine; dmap / dichloromethane / 5 h / Reflux 6: lithium chloride / N,N-dimethyl-formamide / 8 h / 50 °C View Scheme

4-chloro-6-nitro-1,3-benzenediacetic acid → 6-chloro-5-(2-chloroethyl)-2-oxindole (118289-55-7)

Conditions	Yield
Multi-step reaction with 4 steps 1: thionyl chloride / 4 h / 20 °C 2: acetic acid; hydrogen / 3 h / 20 °C / 2327.23 Torr 3: sodium tetrahydroborate; lithium bromide; Trimethyl borate / tetrahydrofuran / 18 h / Reflux 4: triphenylphosphine / tetrahydrofuran; tetrachloromethane / 3 h / Reflux View Scheme
Multi-step reaction with 5 steps 1: thionyl chloride / 4 h / 20 °C 2: acetic acid; hydrogen / 3 h / 20 °C / 2327.23 Torr 3: sodium tetrahydroborate; lithium bromide; Trimethyl borate / tetrahydrofuran / 18 h / Reflux 4: triethylamine; dmap / dichloromethane / 5 h / Reflux 5: lithium chloride / N,N-dimethyl-formamide / 8 h / 50 °C View Scheme

dimethyl 4-chloro-6-nitro-1,3-benzenediacetate → 6-chloro-5-(2-chloroethyl)-2-oxindole (118289-55-7)

Conditions	Yield
Multi-step reaction with 3 steps 1: acetic acid; hydrogen / 3 h / 20 °C / 2327.23 Torr 2: sodium tetrahydroborate; lithium bromide; Trimethyl borate / tetrahydrofuran / 18 h / Reflux 3: triphenylphosphine / tetrahydrofuran; tetrachloromethane / 3 h / Reflux View Scheme
Multi-step reaction with 4 steps 1: acetic acid; hydrogen / 3 h / 20 °C / 2327.23 Torr 2: sodium tetrahydroborate; lithium bromide; Trimethyl borate / tetrahydrofuran / 18 h / Reflux 3: triethylamine; dmap / dichloromethane / 5 h / Reflux 4: lithium chloride / N,N-dimethyl-formamide / 8 h / 50 °C View Scheme

methyl 6-chloro-(2-oxindol-5-yl)acetate → 6-chloro-5-(2-chloroethyl)-2-oxindole (118289-55-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium tetrahydroborate; lithium bromide; Trimethyl borate / tetrahydrofuran / 18 h / Reflux 2: triphenylphosphine / tetrahydrofuran; tetrachloromethane / 3 h / Reflux View Scheme
Multi-step reaction with 3 steps 1: sodium tetrahydroborate; lithium bromide; Trimethyl borate / tetrahydrofuran / 18 h / Reflux 2: triethylamine; dmap / dichloromethane / 5 h / Reflux 3: lithium chloride / N,N-dimethyl-formamide / 8 h / 50 °C View Scheme

2,4,5-Trichloronitrobenzene (89-69-0) → 6-chloro-5-(2-chloroethyl)-2-oxindole (118289-55-7)

Conditions	Yield
Multi-step reaction with 7 steps 1: potassium fluoride / N,N-dimethyl-formamide / 12 h / 125 °C / Inert atmosphere 2: N,N-dimethyl-formamide / 12 h / 100 °C 3: hydrogenchloride; acetic acid / water / 18 h / Reflux 4: thionyl chloride / 4 h / 20 °C 5: acetic acid; hydrogen / 3 h / 20 °C / 2327.23 Torr 6: sodium tetrahydroborate; lithium bromide; Trimethyl borate / tetrahydrofuran / 18 h / Reflux 7: triphenylphosphine / tetrahydrofuran; tetrachloromethane / 3 h / Reflux View Scheme
Multi-step reaction with 8 steps 1: potassium fluoride / N,N-dimethyl-formamide / 12 h / 125 °C / Inert atmosphere 2: N,N-dimethyl-formamide / 12 h / 100 °C 3: hydrogenchloride; acetic acid / water / 18 h / Reflux 4: thionyl chloride / 4 h / 20 °C 5: acetic acid; hydrogen / 3 h / 20 °C / 2327.23 Torr 6: sodium tetrahydroborate; lithium bromide; Trimethyl borate / tetrahydrofuran / 18 h / Reflux 7: triethylamine; dmap / dichloromethane / 5 h / Reflux 8: lithium chloride / N,N-dimethyl-formamide / 8 h / 50 °C View Scheme

3-(1-piperazinyl)-1,2-benzisothiazole (87691-87-0) + 6-chloro-5-(2-chloroethyl)-2-oxindole (118289-55-7) → ziprazidone (122883-93-6, 199191-69-0)

Conditions	Yield
With Morwet D425 In water Reflux; Inert atmosphere;	92%
In water Inert atmosphere; Reflux; dispersing agent;	92%
With potassium carbonate; potassium iodide In sulfolane at 75 - 100℃; for 2h; Product distribution / selectivity;	75%

3-(1-piperazinyl)-1,2-benzoisothiazole hydrochloride + 6-chloro-5-(2-chloroethyl)-2-oxindole (118289-55-7) → ziprazidone (122883-93-6, 199191-69-0)

Conditions	Yield
With Morwet D425 In water Product distribution / selectivity; Reflux; Inert atmosphere;	92%
With sodium carbonate In water Product distribution / selectivity; Inert atmosphere; Reflux; Morwet D425;	90%
Stage #1: 3-(piperazin-1-yl)-1,2-benzisothiazole hydrochloride With potassium carbonate In acetonitrile for 0.5h; Stage #2: 6-chloro-5-(2-chloroethyl)-2-oxindole With sodium iodide In acetonitrile for 2h; Reflux;	767 g

6-chloro-5-(2-chloroethyl)-2-oxindole (118289-55-7) + 7-bromo-3-piperazinyl-1,2-benzisothiazole (155167-98-9) → 5-(2-(4-(7-bromo-1,2-benzisothiazol-3-yl)piperazinyl)-ethyl)-6-chloro-1,3-dihydro-2H-indol-2-one (155167-99-0)

Conditions	Yield
With sodium carbonate In water at 115℃; for 20h;	89%

3-(1-piperazinyl)-1,2-benzisothiazole hydrochloride (87691-88-1) + 6-chloro-5-(2-chloroethyl)-2-oxindole (118289-55-7) → ziprazidone (122883-93-6, 199191-69-0)

Conditions	Yield
With sodium carbonate In 1-methyl-pyrrolidin-2-one at 130 - 135℃; for 24h; Product distribution / selectivity;	88.2%
With sodium carbonate In poly(ethylene glycol) methyl ether at 120 - 125℃; for 48h; Product distribution / selectivity;	88%
With sodium carbonate; sodium iodide In toluene for 22.5h; Product distribution / selectivity; Heating / reflux;	86%

4-(benzo[b]thiophen-4-yl)piperidine trifluoroacetate + 6-chloro-5-(2-chloroethyl)-2-oxindole (118289-55-7) → 5-(2-(4-(benzo[b]thiophen-4-yl)piperidin-1-yl)ethyl)-6-chloroindolin-2-one

Conditions	Yield
With potassium carbonate; potassium iodide In water at 105℃; for 12h;	58%

1-(2,3-dihydrobenzo[b]thiophen-4-yl)piperazine hydrochloride + 6-chloro-5-(2-chloroethyl)-2-oxindole (118289-55-7) → 6-chloro-5-(2-(4-(2,3-dihydrobenzo[b]thiophen-4-yl)piperazin-1-yl)ethyl)indolin-2-one

Conditions	Yield
With potassium carbonate; potassium iodide In acetonitrile at 85℃;	56%

1-(benzo[b]thiophen-4-yl)piperazine hydrochloride + 6-chloro-5-(2-chloroethyl)-2-oxindole (118289-55-7) → 5-(2-(4-(benzo[b]thiophen-4-yl)piperazin-1-yl)ethyl)-6-chloroindolin-2-one hydrochloride

Conditions	Yield
With sodium carbonate; sodium iodide In water for 24h; Reflux;	51%

4-(piperazin-1-yl)thieno[2,3-c]pyridine trifluoroacetate + 6-chloro-5-(2-chloroethyl)-2-oxindole (118289-55-7) → 6-chloro-5-(2-(4-(thieno[2,3-c]pyridin-4-yl)piperazin-1-yl)ethyl)indolin-2-one

Conditions	Yield
With potassium carbonate; potassium iodide In acetonitrile at 80℃;	8.7%

3-(1-piperazinyl)-1,2-benzisothiazole (87691-87-0) + acetone (67-64-1) + 6-chloro-5-(2-chloroethyl)-2-oxindole (118289-55-7) → 5-[2-(4-1,2-benzisothiazol-3-yl-piperazin-1-yl)ethyl]-6-chloro-3-isopropylidene-1,3-dihydro-indol-2-one

Conditions	Yield
With potassium carbonate In water at 100℃; for 24h; Heating / reflux;	3%

6-chloro-5-(2-chloro-1-hydroxyethyl) indolin-2-one (884305-06-0) + 3-(1-piperazinyl)-1,2-benzisothiazole (87691-87-0) + 6-chloro-5-(2-chloroethyl)-2-oxindole (118289-55-7) + 6-chloro-5-(2-chloroacetyl) indolin-2-one (118307-04-3) → 5-(2-(4-(1,2-benzisothiazole-3-yl)-1-piperazinyl)-1-hydroxyethyl)-6-chloro-1,3-dihydro-2H-indole-2-one (884305-08-2) + 5-(2-(4-(1,2-benzisothiazole-3-yl)-1-piperazinyl)-1-oxoethyl)-6-chloro-1,3-dihydro-2H-indole-2-one (884305-07-1) + ziprazidone (122883-93-6, 199191-69-0)

Conditions	Yield
With tetrabutylammomium bromide; sodium carbonate; sodium iodide In cyclohexane Heating / reflux;

4-trimethylsilyl-1-(benzo[d]isothiazol-3-yl)piperazine + 6-chloro-5-(2-chloroethyl)-2-oxindole (118289-55-7) → ziprazidone (122883-93-6, 199191-69-0)

Conditions	Yield
With water; sodium carbonate; sodium iodide In N,N-dimethyl-formamide at 110℃; for 0.5h; Product distribution / selectivity;
With water; sodium carbonate; sodium iodide at 95 - 100℃; for 7.66667h; Product distribution / selectivity;

3-(1-piperazinyl)-1,2-benzisothiazole (87691-87-0) + 6-chloro-5-(2-chloroethyl)-2-oxindole (118289-55-7) → ziprasidone hydrochloride

Conditions	Yield
Stage #1: 3-(1-piperazinyl)-1,2-benzisothiazole; 6-chloro-5-(2-chloroethyl)-2-oxindole With sodium carbonate; sodium iodide In water; dimethyl sulfoxide at 115 - 125℃; for 2.75h; Stage #2: With hydrogenchloride In water for 0.166667h;

1-(benzo[d]isoxazol-3-yl)piperazine hydrochloride (87691-90-5) + 6-chloro-5-(2-chloroethyl)-2-oxindole (118289-55-7) → 5-(2-(4-(1,2-benziso-thiazol-3-yl)piperazinyl)ethyl)-6-chloro-1,3-dihydro-2H-indol-2-one

Conditions	Yield
Stage #1: 1-(benzo[d]isoxazol-3-yl)piperazine hydrochloride With sodium carbonate In water at 20℃; for 1h; Stage #2: 6-chloro-5-(2-chloroethyl)-2-oxindole With sodium iodide In water at 20 - 90℃; for 21 - 31h; Stage #3: In water at 45 - 80℃; for 1h; Product distribution / selectivity;

Upstream product

• 884305-06-0 6-chloro-5-(2-chloro-1-hydroxyethyl) indolin-2-one 
• 89-69-0 2,4,5-Trichloronitrobenzene 
• 510703-85-2 6-chloro-5-(2-hydroxyethyl)-2-oxindole 
• 510703-84-1 methyl 6-chloro-(2-oxindol-5-yl)acetate 
• 510703-81-8 4-chloro-6-nitro-1,3-benzenediacetic acid 
• 1481-68-1 5-chloro-2,4-difluoronitrobenzene 
• 56341-37-8 6-chloro-2-oxindole 
• 118307-04-3 6-chloro-5-(2-chloroacetyl) indolin-2-one 
• 147124-32-1 dimethyl (4-chloro-2-nitrophenyl)malonate 
• 89-61-2 2,5-dichloronitrobenzene 

Downstream Products

• 122883-93-6 ziprazidone 
• 884305-08-2 5-(2-(4-(1,2-benzisothiazole-3-yl)-1-piperazinyl)-1-hydroxyethyl)-6-chloro-1,3-dihydro-2H-indole-2-one 
• 884305-07-1 5-(2-(4-(1,2-benzisothiazole-3-yl)-1-piperazinyl)-1-oxoethyl)-6-chloro-1,3-dihydro-2H-indole-2-one 
• 684269-12-3 5-[2-(4-1,2-benzisothiazol-3-yl-piperazin-1-yl)ethyl]-6-chloro-3-isopropylidene-1,3-dihydro-indol-2-one 

Relevant articles and documents

Improved process for the preparation of 6-chloro-5-(2-chloroethyl)oxindole

The current process for ziprasidone involves preparation and isolation of the key intermediate 6-chloro-5-(2-chloroethyl)oxindole. An improved process for the synthesis of this intermediate is reported here. The new process involves use of a novel Lewis acid-mediated selective deoxygenation of the precursor ketone with tetramethyldisiloxane. The new method affords the desired compound in a one-pot process obviating the need for isolation of the potentially hazardous precursor ketone. This process was successfully scaled up to multikilo scale.

Process for the preparation of ziprasidone

A process for the preparation of ziprasidone and a novel intermediate useful in its preparation. The process comprises the reduction of a compound (III) to give a compound (V) which is then reduced to compound (II). This is reacted with compound (IV) to give the desired compound.

Ziprasidone process

A process for preparing ziprasidone having low levels of keto ziprasidone and hydroxy ziprasidone impurities.