58113-30-7

Basic information

• Product Name: 4-(3-chloropropoxy)-3-methoxyacetophenone
• Synonyms: 4-(3-chloropropoxy)-3-methoxyacetophenone;1-[4-(3-Chloropropoxy)-3-methoxyphenyl]ethan-1-one;3-(4-Acetyl-2-Methoxyphenoxy)propyl Chloride;Ethanone,1-[4-(3-chloropropoxy)-3-Methoxyphenyl]-;Iloperidone Chloropropoxy Impurity;1-(4-(3-Chloropropoxy)
• CAS NO: 58113-30-7
• Molecular Formula: C₁₂H₁₅ClO₃
• Molecular Weight: 242.6987
• EINECS: -0
• Product Categories: Aromatics;Intermediates & Fine Chemicals;Pharmaceuticals;Iloperidone Intermediate
• Mol File: 58113-30-7.mol
• Article Data: 57

Chemical Properties

• Boiling Point: 367 °C at 760 mmHg
• Flash Point: 149.8 °C
• Appearance: White solid
• Density: 1.137 g/cm³
• Vapor Pressure: 1.4E-05mmHg at 25°C
• Refractive Index: 1.509
• Storage Temp.: Sealed in dry,Room Temperature
• CAS DataBase Reference: 4-(3-chloropropoxy)-3-methoxyacetophenone(CAS DataBase Reference)
• NIST Chemistry Reference: 4-(3-chloropropoxy)-3-methoxyacetophenone(58113-30-7)
• EPA Substance Registry System: 4-(3-chloropropoxy)-3-methoxyacetophenone(58113-30-7)

Safety Data

• HazardClass: IRRITANT
• Hazardous Substances Data: 58113-30-7(Hazardous Substances Data)

Usage

Chemical Properties

White Solid

Uses

Intermediate in the production of Iloperidone

InChI:InChI=1/C12H15ClO3/c1-9(14)10-4-5-11(12(8-10)15-2)16-7-3-6-13/h4-5,8H,3,6-7H2,1-2H3

Synthetic route

1,3-chlorobromopropane (109-70-6) + 1-(3-methoxy-4-hydroxyphenyl)ethanone (498-02-2) → 4-(3-chloropropoxy)-3-methoxyacetophenone (58113-30-7)

Conditions	Yield
With potassium carbonate In acetonitrile at 20 - 80℃; for 3h;	95%
With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 10h;	93.8%
With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 10h;	93.8%

1,3-chlorobromopropane (109-70-6) + 1-(3-methoxy-4-hydroxyphenyl)ethanone (498-02-2) → 4-(3-chloropropoxy)-3-methoxyacetophenone (58113-30-7) + 1,1'-(4,4'-(propane-1,3-diylbis(oxy))bis(3-methoxy-4,1-phenylene))diethanone (19417-90-4)

Conditions	Yield
With potassium carbonate In acetone for 20h; Reflux;	A 85% B 7%

1-(4-(3-chloropropoxy)-3-methoxyphenyl)ethanol (1308246-54-9) → 4-(3-chloropropoxy)-3-methoxyacetophenone (58113-30-7)

Conditions	Yield
With pyridine; chromium(VI) oxide In dichloromethane; toluene at 30℃; Product distribution / selectivity;	82%
With potassium dichromate; sulfuric acid In diethyl ether; water at 10 - 20℃; for 2h; Product distribution / selectivity;

methyl magnesium iodide (917-64-6) + 4-(3-chloropropoxy)-3-methoxybenzonitrile (210918-52-8) → 4-(3-chloropropoxy)-3-methoxyacetophenone (58113-30-7)

Conditions	Yield
Stage #1: methyl magnesium iodide; 4-(3-chloropropoxy)-3-methoxybenzonitrile With copper(l) chloride In diethyl ether; toluene for 1h; Inert atmosphere; Reflux; Stage #2: With sulfuric acid; water In toluene at 25℃; for 2.25h; Product distribution / selectivity; Reflux;	77.5%

4-(3-chloropropoxy)-3-methoxybenzonitrile (210918-52-8) + methyl iodide (74-88-4) → 4-(3-chloropropoxy)-3-methoxyacetophenone (58113-30-7)

Conditions	Yield
Stage #1: methyl iodide With magnesium In diethyl ether for 0.5h; Reflux; Stage #2: 4-(3-chloropropoxy)-3-methoxybenzonitrile In toluene for 3h; Reflux; Stage #3: With hydrogenchloride; water at 0℃; for 6h; Reflux;	75%

potassium carbonate (584-08-7) + 1,3-chlorobromopropane (109-70-6) + 1-(3-methoxy-4-hydroxyphenyl)ethanone (498-02-2) → 4-(3-chloropropoxy)-3-methoxyacetophenone (58113-30-7)

Conditions	Yield
In acetone

3-methoxy-4-(3-chloropropoxy) benzaldehyde (151719-92-5) → 4-(3-chloropropoxy)-3-methoxyacetophenone (58113-30-7)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: magnesium / diethyl ether / 1 h / Reflux 1.2: 6 h / 0 °C / Reflux 1.3: Cooling with ice 2.1: potassium dichromate; sulfuric acid / diethyl ether; water / 2 h / 10 - 20 °C View Scheme
Multi-step reaction with 2 steps 1.1: hydroxylamine hydrochloride; sodium formate; formic acid / 1 h / Reflux 2.1: magnesium / diethyl ether / 0.5 h / Reflux 2.2: 3 h / Reflux 2.3: 6 h / 0 °C / Reflux View Scheme
Multi-step reaction with 2 steps 1.1: hydroxylamine hydrochloride; sodium formate; formic acid / 1 h / Reflux 2.1: copper(l) chloride / toluene; diethyl ether / 1 h / Inert atmosphere; Reflux 2.2: 2.25 h / 25 °C / Reflux View Scheme

vanillin (121-33-5) → 4-(3-chloropropoxy)-3-methoxyacetophenone (58113-30-7)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: potassium carbonate / acetone / Reflux 2.1: magnesium / diethyl ether / 1 h / Reflux 2.2: 6 h / 0 °C / Reflux 2.3: Cooling with ice 3.1: potassium dichromate; sulfuric acid / diethyl ether; water / 2 h / 10 - 20 °C View Scheme

3-methoxy-4-hydroxybenzonitrile (4421-08-3) → 4-(3-chloropropoxy)-3-methoxyacetophenone (58113-30-7)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: potassium carbonate / acetone / 0.08 h / 25 - 30 °C 1.2: 12.5 h / 25 - 30 °C / Reflux 2.1: magnesium / diethyl ether / 0.5 h / Reflux 2.2: 3 h / Reflux 2.3: 6 h / 0 °C / Reflux View Scheme
Multi-step reaction with 2 steps 1.1: potassium carbonate / acetone / 0.08 h / 25 - 30 °C 1.2: 12.5 h / 25 - 30 °C / Reflux 2.1: copper(l) chloride / toluene; diethyl ether / 1 h / Inert atmosphere; Reflux 2.2: 2.25 h / 25 °C / Reflux View Scheme

1,3-chlorobromopropane (109-70-6) + 1-(3-methoxy-4-hydroxyphenyl)ethanone (498-02-2) → 4-(3-chloropropoxy)-3-methoxyacetophenone (58113-30-7) + 1-(4-(3-bromopropoxy)-3-methoxyphenyl)ethanone (3245-49-6)

Conditions	Yield
With tetrabutylammomium bromide; potassium carbonate In acetonitrile at 80℃; Industry scale;

4-(3-chloropropoxy)-3-methoxyacetophenone (58113-30-7) + 6-fluoro-3-(piperidin-4-yl)benzo[d]isoxazole hydrochloride (84163-13-3) → iloperidone (133454-47-4)

Conditions	Yield
Stage #1: 6-fluoro-3-(piperidin-4-yl)benzo[d]isoxazole hydrochloride With sodium hydroxide In water at 25 - 30℃; for 0.25h; Industrial scale; Green chemistry; Stage #2: 4-(3-chloropropoxy)-3-methoxyacetophenone In water at 25 - 30℃; for 0.25h; Industrial scale; Green chemistry; Stage #3: With tetrabutylammomium bromide In n-heptane; water at 65 - 70℃; Reagent/catalyst; Solvent; Temperature; Concentration; Time; Industrial scale; Green chemistry;	95%
With sodium hydrogencarbonate In toluene; acetonitrile at 76℃; for 6h; Temperature;	90.5%
With potassium carbonate In N,N-dimethyl-formamide at 90℃; for 16h;

6-fluoro-2-(piperidin-4-yl)-1,3-benzoxazole (335079-99-7) + 4-(3-chloropropoxy)-3-methoxyacetophenone (58113-30-7) → iloperidone

Conditions	Yield
With triethylamine In water at 60 - 65℃; for 14h;	95%

4-(3-chloropropoxy)-3-methoxyacetophenone (58113-30-7) → 1-(4-(3-chloropropoxy)-5-methoxy-2-nitrophenyl)ethan-1-one (1160707-44-7)

Conditions	Yield
With nitric acid In dichloromethane at -20 - -10℃; for 2h;	89%
With nitric acid In dichloromethane at -20 - -10℃; for 2h;	89%
With nitric acid In dichloromethane at -20 - -10℃; for 2h;	89%

4-(3-chloropropoxy)-3-methoxyacetophenone (58113-30-7) → 1-(4-(3-chloropropoxy)-5-methoxy-2-nitro)acetophenone

Conditions	Yield
With nitric acid In dichloromethane at -20 - -10℃; for 3h;	89%

4-(3-chloropropoxy)-3-methoxyacetophenone (58113-30-7) + 6-fluoro-3-(piperidin-4-yl)benzo[d]isoxazole hydrochloride (84163-13-3) → iloperidone

Conditions	Yield
With potassium carbonate; potassium iodide In ethyl acetate; N,N-dimethyl-formamide at 80℃; for 50h; Inert atmosphere;	84.65%

4-phenylpiperidine (771-99-3) + 4-(3-chloropropoxy)-3-methoxyacetophenone (58113-30-7) → 1-{3-Methoxy-4-[3-(4-phenyl-piperidin-1-yl)-propoxy]-phenyl}-ethanone; hydrochloride (117022-90-9)

Conditions	Yield
With sodium carbonate; potassium iodide In butan-1-ol Heating;	82%

1-phenylmethylpiperazine (2759-28-6) + 4-(3-chloropropoxy)-3-methoxyacetophenone (58113-30-7) + maleic acid (110-16-7) → 1-{4-[3-(4-Benzyl-piperazin-1-yl)-propoxy]-3-methoxy-phenyl}-ethanone; compound with (Z)-but-2-enedioic acid (117022-96-5)

Conditions	Yield
With sodium carbonate; potassium iodide 1) n-butanol, reflux;	80%

4-(3-chloropropoxy)-3-methoxyacetophenone (58113-30-7) + α-<3-(ethylamino)propyl>-4-fluoro-α-(4-fluorophenyl)benzenemethanol (117022-82-9) → 1-[4-(3-{[4,4-Bis-(4-fluoro-phenyl)-4-hydroxy-butyl]-ethyl-amino}-propoxy)-3-methoxy-phenyl]-ethanone (117023-21-9)

Conditions	Yield
With sodium carbonate; potassium iodide In butan-1-ol Heating;	80%

4-(3-chloropropoxy)-3-methoxyacetophenone (58113-30-7) + [α,α-bis(4-fluorophenyl)]-3-piperidinemethanol (117022-69-2) → 1-[4-[3-[3-[Bis(4-fluorophenyl)hydroxymethyl]-1-piperidinyl]propoxy]-3-methoxyphenyl]ethanone (117023-16-2)

Conditions	Yield
With sodium carbonate; potassium iodide In butan-1-ol Heating;	78%
With potassium iodide; sodium carbonate In butan-1-ol	4.0 g (78%)

piperidine (110-89-4) + 4-(3-chloropropoxy)-3-methoxyacetophenone (58113-30-7) + (2E)-but-2-enedioic acid (110-17-8) → 1-[3-Methoxy-4-(3-piperidin-1-yl-propoxy)-phenyl]-ethanone; compound with (E)-but-2-enedioic acid (117022-84-1)

Conditions	Yield
With sodium carbonate; potassium iodide 1) n-butanol, reflux;	77%

4-(3-chloropropoxy)-3-methoxyacetophenone (58113-30-7) + 1,1-bis(4-fluorophenyl)-1-(4-piperidinyl)methanol (60284-98-2) → AHR 5333 (60284-71-1)

Conditions	Yield
With sodium carbonate; potassium iodide In butan-1-ol for 20h; Heating;	75%
With sodium hydrogencarbonate In N-methyl-acetamide; benzene

4-(3-chloropropoxy)-3-methoxyacetophenone (58113-30-7) + 4-[(Cyclohexyl)(4-fluorophenyl)methyl]piperidine (131912-01-1) → 1-[4-[3-[4-[Cyclohexyl(4-fluorophenyl)methyl]-1-piperidinyl]propoxy]-3-methoxyphenyl]ethanone (131911-58-5)

Conditions	Yield
With potassium carbonate; potassium iodide In butan-1-ol Heating;	74%

4-phenyl-1-piperazine (92-54-6) + 4-(3-chloropropoxy)-3-methoxyacetophenone (58113-30-7) → 1-{3-Methoxy-4-[3-(4-phenyl-piperazin-1-yl)-propoxy]-phenyl}-ethanone (117022-97-6)

Conditions	Yield
With sodium carbonate; potassium iodide In butan-1-ol Heating;	73%

4-(3-chloropropoxy)-3-methoxyacetophenone (58113-30-7) + α,α-bis(3-fluorophenyl)-4-piperidinemethanol (117022-55-6) → 1-[3-(4-acetyl-2-methoxyphenoxy)propyl]-α,α-bis(3-fluorophenyl)-4-piperidinemethanol (117023-23-1)

Conditions	Yield
With sodium carbonate; potassium iodide In butan-1-ol Heating;	71%

4-(3-chloropropoxy)-3-methoxyacetophenone (58113-30-7) + oxalic acid (144-62-7) + 4-(diphenylmethoxymethyl)piperidine (117022-66-9) → 1-(3-Methoxy-4-{3-[4-(methoxy-diphenyl-methyl)-piperidin-1-yl]-propoxy}-phenyl)-ethanone; compound with oxalic acid (117022-92-1)

Conditions	Yield
With sodium carbonate; potassium iodide 1) n-butanol, reflux;	71%

4-(3-chloropropoxy)-3-methoxyacetophenone (58113-30-7) + α,α-bis(4-fluorophenyl)-3-pyrrolidineacetonitrile (131912-08-8) → 1-[3-(4-Acetyl-2-methoxyphenoxy)propyl]-α,α-bis(4-fluorophenyl)-3-pyrrolidineacetonitrile (131950-22-6)

Conditions	Yield
With potassium carbonate; potassium iodide In butan-1-ol Heating;	68%

4-(3-chloropropoxy)-3-methoxyacetophenone (58113-30-7) + 4-benzoylpiperidine (37586-22-4) → 1-{4-[3-(4-benzoyl-piperidin-1-yl)-propoxy]-3-methoxy-phenyl}-ethanone (117022-85-2)

Conditions	Yield
With sodium carbonate; potassium iodide In butan-1-ol Heating;	66%

4-(3-chloropropoxy)-3-methoxyacetophenone (58113-30-7) + (2E)-but-2-enedioic acid (110-17-8) + α,α-bis(4-fluorophenyl)-4-piperidineethanol (107071-83-0) → 1-[4-(3-{4-[2,2-Bis-(4-fluoro-phenyl)-2-hydroxy-ethyl]-piperidin-1-yl}-propoxy)-3-methoxy-phenyl]-ethanone; compound with (E)-but-2-enedioic acid (117023-15-1)

Conditions	Yield
With sodium carbonate; potassium iodide 1) n-butanol, reflux;	65%

4-(3-chloropropoxy)-3-methoxyacetophenone (58113-30-7) + 1,2-Bis-(4-fluoro-phenyl)-1-piperidin-4-yl-ethanol (117022-58-9) → 1-[4-(3-{4-[1,2-Bis-(4-fluoro-phenyl)-1-hydroxy-ethyl]-piperidin-1-yl}-propoxy)-3-methoxy-phenyl]-ethanone (117023-26-4)

Conditions	Yield
With sodium carbonate; potassium iodide In butan-1-ol Heating;	64%

4-(3-chloropropoxy)-3-methoxyacetophenone (58113-30-7) + phenyl-piperidin-4-yl-methanol (38081-60-6) → 1-(4-{3-[4-(Hydroxy-phenyl-methyl)-piperidin-1-yl]-propoxy}-3-methoxy-phenyl)-ethanone (117022-86-3)

Conditions	Yield
With sodium carbonate; potassium iodide In butan-1-ol Heating;	64%

4-(3-chloropropoxy)-3-methoxyacetophenone (58113-30-7) + 4-(Diphenylmethyl)piperidine (19841-73-7) + oxalic acid (144-62-7) → 1-[4-[3-[4-(Diphenylmethyl)-1-piperidinyl]propoxy]-3-methoxyphenyl]ethanone oxalate (60284-70-0)

Conditions	Yield
With sodium carbonate; potassium iodide 1) n-butanol, reflux;	64%

4-(3-chloropropoxy)-3-methoxyacetophenone (58113-30-7) + oxalic acid (144-62-7) + N-Benzoylpiperazine (13754-38-6) → 1-{4-[3-(4-Benzoyl-piperazin-1-yl)-propoxy]-3-methoxy-phenyl}-ethanone; compound with oxalic acid (117022-94-3)

Conditions	Yield
With sodium carbonate; potassium iodide 1) n-butanol, reflux;	63%

4-(3-chloropropoxy)-3-methoxyacetophenone (58113-30-7) + 2-[(4-Fluoro-phenyl)-piperidin-4-yl-methyl]-pyridine (131911-87-0) → 1-[4-[3-[4-[(4-fluorophenyl)(2-pyridinyl)methyl]-1-piperidinyl]propoxy]-3-methoxyphenyl]ethanone (131911-41-6)

Conditions	Yield
With potassium carbonate; potassium iodide In butan-1-ol Heating;	62%

4-benzylpyperidine (31252-42-3) + 4-(3-chloropropoxy)-3-methoxyacetophenone (58113-30-7) + maleic acid (110-16-7) → 1-{4-[3-(4-Benzyl-piperidin-1-yl)-propoxy]-3-methoxy-phenyl}-ethanone; compound with (Z)-but-2-enedioic acid (117022-88-5)

Conditions	Yield
With sodium carbonate; potassium iodide 1) n-butanol, reflux;	60%

4-(3-chloropropoxy)-3-methoxyacetophenone (58113-30-7) + α,α-bis(4-fluorophenyl)-3-piperidinepropanenitrile (131912-12-4) → 1-[3-(4-acetyl-2-methoxyphenoxy)propyl]-α,α-bis(4-fluorophenyl)-3-piperidinepropanenitrile (131911-61-0)

Conditions	Yield
With potassium carbonate; potassium iodide In butan-1-ol Heating;	60%

Upstream product

• 210918-52-8 4-(3-chloropropoxy)-3-methoxybenzonitrile 
• 74-88-4 methyl iodide 
• 917-64-6 methyl magnesium iodide 
• 4421-08-3 3-methoxy-4-hydroxybenzonitrile 
• 109-70-6 1.3-chlorobromopropane 
• 498-02-2 1-(3-methoxy-4-hydroxyphenyl)ethanone 
• 1308246-54-9 1-[4-(3-chloropropoxy)-3-methoxyphenyl]ethanol 
• 121-33-5 vanillin 
• 151719-92-5 3-methoxy-4-(3-chloropropoxy) benzaldehyde 
• 584-08-7 potassium carbonate 

Downstream Products

• 60284-76-6 1-[4-[3-[4-(Diphenylhydroxymethyl)-1-piperidinyl]propoxy]-3-methoxyphenyl]ethanone oxalate 
• 133454-46-3 1-[4-[3-[4-(1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-3-methoxyphenyl]ethanone 
• 133454-47-4 iloperidone 
• 150039-94-4 1-[4-[3-[4-[(4-Fluorophenyl)[(2-phenylethyl)amino]methyl]-1-piperidinyl]propoxy]-3-methoxyphenyl]ethanone (E)-2-butenedioate 
• 70829-35-5 1-[3-(p-Acetyl-o-methoxyphenoxy)-propyl]-4-(p-fluorobenzoyl)-4-hydroxy-piperidine hydrochloride 
• 117023-18-4 1-[4-(3-{3-[2,2-Bis-(4-fluoro-phenyl)-2-hydroxy-ethyl]-piperidin-1-yl}-propoxy)-3-methoxy-phenyl]-ethanone; compound with (E)-but-2-enedioic acid 
• 117023-15-1 1-[4-(3-{4-[2,2-Bis-(4-fluoro-phenyl)-2-hydroxy-ethyl]-piperidin-1-yl}-propoxy)-3-methoxy-phenyl]-ethanone; compound with (E)-but-2-enedioic acid 
• 117039-49-3 1-[4-(3-{4-[Bis-(4-chloro-phenyl)-hydroxy-methyl]-piperidin-1-yl}-propoxy)-3-methoxy-phenyl]-ethanone; compound with oxalic acid 
• 117022-92-1 1-(3-Methoxy-4-{3-[4-(methoxy-diphenyl-methyl)-piperidin-1-yl]-propoxy}-phenyl)-ethanone; compound with oxalic acid 

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