953789-37-2

Basic information

• Product Name: 1-[[2-(4-Chlorophenyl)ethyl]amino]-2-chloropropane
• Synonyms: 1-[[2-(4-Chlorophenyl)ethyl]amino]-2-chloropropane;1-[[2-(4-Chlorophenyl)ethyl]amino]-2-chloropropane Hydrochloride;2-Chloro-N-(4-chlorophenethyl)propan-1-aMine hydrochloride;BenzeneethanaMine, 4-chloro-N-(2-chloropropyl)-, hydrochloride (1:1);2-chloro-N-(4-chlorophenethyl)propan-1-aMin hydrochloride;Lorcaserin interMediate;Lorcaserin iMpurity B;2-chloro-N-(4-chlorophenethyl)propan-1-aMiniuM chloride
• CAS NO: 953789-37-2
• Molecular Formula: C11H15Cl2N
• Molecular Weight: 268.61
• EINECS: 1308068-626-2
• Product Categories: 5-HT 2c receptor agonist
• Mol File: 953789-37-2.mol
• Article Data: 12

Chemical Properties

• Appearance: /
• Storage Temp.: Sealed in dry,Room Temperature
• CAS DataBase Reference: 1-[[2-(4-Chlorophenyl)ethyl]amino]-2-chloropropane(CAS DataBase Reference)
• NIST Chemistry Reference: 1-[[2-(4-Chlorophenyl)ethyl]amino]-2-chloropropane(953789-37-2)
• EPA Substance Registry System: 1-[[2-(4-Chlorophenyl)ethyl]amino]-2-chloropropane(953789-37-2)

Safety Data

• Hazardous Substances Data: 953789-37-2(Hazardous Substances Data)

Usage

Uses

4-Chloro-N-(2-chloropropyl)benzeneethanamine Hydrochloride is used as a reagent in the synthesis of Lorcaserin (L469890, HCl); a novel selective 5-HT2C-receptor agonist for the treatment of obesity.

InChI:InChI=1/C11H15Cl2N.ClH/c1-9(12)8-14-7-6-10-2-4-11(13)5-3-10;/h2-5,9,14H,6-8H2,1H3;1H

Synthetic route

4-chloro-N-(2-chloro-1-oxopropyl)benzeneacetamide → 1-((2-(4-chlorophenyl)ethyl)amino)-2-chloropropane hydrochloride (953789-37-2)

Conditions	Yield
With aluminum (III) chloride; sodium tetrahydroborate; chloro-trimethyl-silane In tetrahydrofuran at 70℃; for 24h; Inert atmosphere;	96%

1-[[2-(4-chlorophenyl)ethyl]amino]-2-hydroxypropane (847063-13-2) → 1-((2-(4-chlorophenyl)ethyl)amino)-2-chloropropane hydrochloride (953789-37-2)

Conditions	Yield
With thionyl chloride In N,N-dimethyl acetamide; toluene at 50 - 65℃; for 3h; Inert atmosphere;	88.3%
With thionyl chloride In toluene at 70℃; for 10h;	85%
With thionyl chloride In N,N-dimethyl acetamide; toluene at 45 - 60℃;	81.3%

1-((4-chlorophenethyl)amino)propan-2-ol hydrochloride (1030624-41-9) → 1-((2-(4-chlorophenyl)ethyl)amino)-2-chloropropane hydrochloride (953789-37-2)

Conditions	Yield
With thionyl chloride; N,N-dimethyl acetamide In toluene at 50 - 65℃; for 2.5h; Product distribution / selectivity;	85.82%
With thionyl chloride In N,N-dimethyl acetamide; toluene at 50 - 65℃; Inert atmosphere;	85.66%
With thionyl chloride at 50 - 62℃; for 2h; Product distribution / selectivity; Neat (no solvent);	69.52%

N-(2-(4-chlorophenyl)ethyl)-4-methyl-N-(2-chloropropyl)benzenesulfonamide → 1-((2-(4-chlorophenyl)ethyl)amino)-2-chloropropane hydrochloride (953789-37-2)

Conditions	Yield
With sulfuric acid In water at 120℃; for 2h; Temperature; Reagent/catalyst;	84.7%

4-chlorophenylethylamine (156-41-2) → 1-((2-(4-chlorophenyl)ethyl)amino)-2-chloropropane hydrochloride (953789-37-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium triflate / methanol / 6.5 h / 30 - 60 °C 2: N,N-dimethyl-formamide; thionyl chloride / toluene / 2 h / 45 - 60 °C View Scheme
Multi-step reaction with 2 steps 1: potassium carbonate / acetonitrile / 20 - 60 °C / Inert atmosphere 2: thionyl chloride / N,N-dimethyl acetamide; toluene / 45 - 60 °C View Scheme

2-(4-chlorophenyl)-N-(2-hydroxypropyl)acetamide (1030624-36-2) → 1-((2-(4-chlorophenyl)ethyl)amino)-2-chloropropane hydrochloride (953789-37-2)

Conditions	Yield
Stage #1: 2-(4-chlorophenyl)-N-(2-hydroxypropyl)acetamide With sodium tetrahydroborate; boron trifluoride diethyl etherate In tetrahydrofuran at 0 - 65℃; Inert atmosphere; Stage #2: With hydrogenchloride In water; toluene at 30 - 40℃; for 0.5h;

p-chlorobenzyl cyanide (140-53-4) → 1-((2-(4-chlorophenyl)ethyl)amino)-2-chloropropane hydrochloride (953789-37-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: sodium tetrahydroborate; boron trifluoride diethyl etherate / tetrahydrofuran / 0 - 55 °C / Inert atmosphere 2: potassium carbonate / acetonitrile / 20 - 60 °C / Inert atmosphere 3: thionyl chloride / N,N-dimethyl acetamide; toluene / 45 - 60 °C View Scheme

1-(4-chlorophenyl)-2-((2-hydroxypropyl)amino)ethane-1-one → 1-((2-(4-chlorophenyl)ethyl)amino)-2-chloropropane hydrochloride (953789-37-2)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: sodium tetrahydroborate / 2-methyltetrahydrofuran / 0.25 h / 15 - 20 °C 1.2: 10 h / 60 °C 2.1: thionyl chloride / toluene / 10 h / 70 °C View Scheme

p-chlorophenacyl chloride (937-20-2) → 1-((2-(4-chlorophenyl)ethyl)amino)-2-chloropropane hydrochloride (953789-37-2)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: sodium carbonate / ethanol / 8 h / 60 °C 2.1: sodium tetrahydroborate / 2-methyltetrahydrofuran / 0.25 h / 15 - 20 °C 2.2: 10 h / 60 °C 3.1: thionyl chloride / toluene / 10 h / 70 °C View Scheme

2-(4-Chlorophenyl)ethanol (1875-88-3) → 1-((2-(4-chlorophenyl)ethyl)amino)-2-chloropropane hydrochloride (953789-37-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: hydrogen bromide / 91 - 96 °C / 517.55 - 1807.68 Torr 3: thionyl chloride; N,N-dimethyl acetamide / toluene / 50 - 65 °C View Scheme

2-(4-chlorophenyl)-N-(2-chloropropyl)acetamide → 1-((2-(4-chlorophenyl)ethyl)amino)-2-chloropropane hydrochloride (953789-37-2)

Conditions	Yield
Stage #1: 2-(4-chlorophenyl)-N-(2-chloropropyl)acetamide With sodium tetrahydroborate; boron trifluoride-tetrahydrofuran complex at 60℃; Stage #2: With hydrogenchloride In water for 0.5h; Reflux;	315.2 g

1-((2-(4-chlorophenyl)ethyl)amino)-2-chloropropane hydrochloride (953789-37-2) → (+/-)-Lorcaserin (616201-80-0)

Conditions	Yield
With aluminum (III) chloride In 1,2-dichloro-benzene at 120 - 125℃; Inert atmosphere;	99%
With aluminum (III) chloride at 120 - 125℃; for 3h; Inert atmosphere; Large scale;	97%
With aluminum (III) chloride In 1,2-dichloro-benzene at 135 - 140℃;	96.1%

1-[[2-(4-chlorophenyl)ethyl]amino]-2-hydroxypropane (847063-13-2) + 1-((2-(4-chlorophenyl)ethyl)amino)-2-chloropropane hydrochloride (953789-37-2) → 1-((4-chlorophenethyl)(1-((4-chlorophenethyl)amino)propan-2-yl)amino)propan-2-ol

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 70 - 75℃; for 5h;	22.3%

1-((2-(4-chlorophenyl)ethyl)amino)-2-chloropropane hydrochloride (953789-37-2) + 1,2-dichloro-benzene (95-50-1) → (+/-)-Lorcaserin (616201-80-0)

Conditions	Yield
Stage #1: 1-[[2-(4-chlorophenyl)ethyl]amino]-2-chloropropane hydrochloride; 1,2-dichloro-benzene With aluminum (III) chloride at 126℃; for 16h; Friedel Crafts; Industry scale; Inert atmosphere; Stage #2: With sodium hydroxide In cyclohexane; water pH=12; Product distribution / selectivity; Industry scale;

1-((2-(4-chlorophenyl)ethyl)amino)-2-chloropropane hydrochloride (953789-37-2) → Lorcaserin hydrochloride (846589-98-8)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: aluminum (III) chloride / 1,2-dichloro-benzene / 3 h / 125 - 130 °C 2.1: L-Tartaric acid / acetone; water / 0.5 h / 45 - 50 °C 3.1: potassium carbonate / water / 0.33 h / 10 - 25 °C 3.2: 0 - 5 °C View Scheme

1-((2-(4-chlorophenyl)ethyl)amino)-2-chloropropane hydrochloride (953789-37-2) → bis((R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine) L-(+)-tartarate

Conditions	Yield
Multi-step reaction with 2 steps 1: aluminum (III) chloride / 1,2-dichloro-benzene / 3 h / 125 - 130 °C 2: L-Tartaric acid / acetone; water / 0.5 h / 45 - 50 °C View Scheme

1-((2-(4-chlorophenyl)ethyl)amino)-2-chloropropane hydrochloride (953789-37-2) → 2C11H14ClN*C4H6O6

Conditions	Yield
Multi-step reaction with 2 steps 1: aluminum oxide / 1,2-dichloro-benzene / 130 - 140 °C / Inert atmosphere 2: acetone; water / 0 - 55 °C View Scheme

1-((2-(4-chlorophenyl)ethyl)amino)-2-chloropropane hydrochloride (953789-37-2) → (S)-8-chloro-1-methyl-1,2,4,5-tetrahydro-3H-benzo[d]azepine hydrochloride

Conditions	Yield
Multi-step reaction with 3 steps 1: aluminum oxide / 1,2-dichloro-benzene / 130 - 140 °C / Inert atmosphere 2: acetone; water / 0 - 55 °C 3: potassium carbonate / water; ethyl acetate / 0.5 h / 25 - 30 °C View Scheme

1-((2-(4-chlorophenyl)ethyl)amino)-2-chloropropane hydrochloride (953789-37-2) → lorcaserin

Conditions	Yield
With aluminum (III) chloride In 1,2-dichloro-benzene at 126℃; for 16h; Temperature; Friedel-Crafts Alkylation; Inert atmosphere; Large scale;

Upstream product

• 937-20-2 p-chlorophenacyl chloride 
• 1875-88-3 2-(4-Chlorophenyl)ethanol 
• 140-53-4 p-chlorobenzyl cyanide 
• 1030624-36-2 2-(4-chlorophenyl)-N-(2-hydroxypropyl)acetamide 
• 156-41-2 4-chlorophenylethylamine 
• 847063-13-2 1-[[2-(4-chlorophenyl)ethyl]amino]-2-hydroxypropane 
• 1030624-41-9 1-((4-chlorophenethyl)amino)propan-2-ol hydrochloride 

Downstream Products

• 616201-80-0 (+/-)-Lorcaserin 
• 846589-98-8 Lorcaserin hydrochloride 
• 824430-78-6 bis((R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine) L-(+)-tartarate 
• 824430-78-6 2C₁₁H₁₄ClN*C₄H₆O₆ 
• 1006037-59-7 (S)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-benzo[d]azepine hydrochloride 
• 616202-92-7 lorcaserin 

Relevant articles and documents

Method for preparing lorcaserin

The invention discloses a method for preparing lorcaserin. Specifically, the method comprises the steps: taking p-chlorophenylacetonitrile as an initial raw material, preparing p-chlorophenylethylamine through reduction; carrying out a reaction with p-toluenesulfonyl chloride to form an amino occupying intermediate; enabling the intermediate to carry out a reaction with monochloroacetone under analkaline condition to form N-(2-(4-chlorphenyl)ethyl)-4-methyl-N-(2-propionyl)benzenesulfonamide, and then carrying out reduction, chlorination, p-toluenesulfonyl removal and intramolecular Friedel-Crafts alkylation to synthesize 8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzoazepine, carrying out L-(+)-tartaric acid resolution and alkalization on azepine to remove tartaric acid, and acting with hydrogen chloride diethyl ether to salify to prepare lorcaserin. The method has the characteristics of simple synthesis method, good reaction selectivity, high product purity, environmental protectionand low preparation cost.

Preparation method of key intermediate I of lorcaserin

The invention discloses a preparation method of a key intermediate I of lorcaserin. The preparation method comprises the steps as follows: (1) in an organic solvent A, 2,4'-dichloroacetophenone is subjected to a condensation reaction with isopropanolamine under catalysis of alkali, and 1-(4-chlorophenyl)-2-((2-hydroxypropyl)amino)ethane-1-one is obtained; (2) the 1-(4-chlorophenyl)-2-((2-hydroxypropyl)amino)ethane-1-one obtained in the step (1) is subjected to catalytic reduction with sodium borohydride and acid in a solvent B, and the key intermediate I of lorcaserin is obtained. The preparation method can synthesize the key intermediate I of lorcaserin from cheap and easily available raw materials under mild reaction conditions, has the advantages of being simple to operate, low in costand high in yield, and is energy-saving, environmentally friendly and suitable for mass production.

A Concise Synthesis of Racemic Lorcaserin

We report herein the concise synthesis of racemic lorcaserin (±)-1, which is an anti-obesity drug. The synthetic route involved the key synthesis of an asymmetrical imide intermediate 11 and its efficient reduction. Imide 11 was synthesized directly by the reaction of nitrile 9 with acid 10. The reducing system of NaBH4, AlCl3, and trimethylsilyl chloride efficiently fulfilled the reduction of imide 11 to amine 8a, which could be converted to (±)-1 via Friedel-Crafts reaction as reported. This route afforded 69% two-step yield of 8a from 9 via 11, and the concise synthesis of (±)-1 was completed in three steps. This route offers an alternative pathway to the synthesis of (±)-1 and its analogues.