119356-76-2

Basic information

• Product Name: -[2-1-NAPHTHOXY)ETHYL]BENZYLAMINE / 3-(1-NAPHTHOXY)-1-PHENYL PROPYLAMINE
• Synonyms: -[2-1-NAPHTHOXY)ETHYL]BENZYLAMINE / 3-(1-NAPHTHOXY)-1-PHENYL PROPYLAMINE;N,N-Dimethyl-alpha-[2-(1-naphthalenyloxy)ethyl]benzenemethanamine;N,N-diMethyl-3-(naphthalen-1-yloxy)-1-phenylpropan-1-aMine;-[2-1-PHTHOXY)ETHYL]BENZYLAMINE / 3-(1-PHTHOXY)-1-PHENYL PROPYLAMINE
• CAS NO: 119356-76-2
• Molecular Formula: C₂₁H₂₃NO
• Molecular Weight: 305.419
• Mol File: 119356-76-2.mol
• Article Data: 7

Chemical Properties

• Boiling Point: 454℃
• Flash Point: 132℃
• Appearance: /
• Density: 1.081
• PKA: 8.38±0.50(Predicted)
• CAS DataBase Reference: -[2-1-NAPHTHOXY)ETHYL]BENZYLAMINE / 3-(1-NAPHTHOXY)-1-PHENYL PROPYLAMINE(CAS DataBase Reference)
• NIST Chemistry Reference: -[2-1-NAPHTHOXY)ETHYL]BENZYLAMINE / 3-(1-NAPHTHOXY)-1-PHENYL PROPYLAMINE(119356-76-2)
• EPA Substance Registry System: -[2-1-NAPHTHOXY)ETHYL]BENZYLAMINE / 3-(1-NAPHTHOXY)-1-PHENYL PROPYLAMINE(119356-76-2)

Safety Data

• Hazardous Substances Data: 119356-76-2(Hazardous Substances Data)

Usage

General Description

The chemical -[2-(1-naphthoxy)ethyl]benzylamine, also known as 3-(1-naphthoxy)-1-phenylpropylamine, is a compound that belongs to the family of organic compounds known as alpha-arylamines. It consists of a benzylamine molecule substituted by a 1-naphthoxy group at the ethylamine tail. This chemical compound has a wide range of potential pharmacological and biological activities, including its use as a structural moiety in the development of new drugs and pharmaceuticals. It has been studied for its potential applications in the treatment of various medical conditions and is also used as a precursor in the synthesis of other compounds with similar properties.

Synthetic route

3-((4-bromonaphthalene-1-yl)oxy)-N,N-dimethyl-1-phenyl-prop-1-amine → N,N-dimethylamino-3-(naphthyl-1-oxy)-1-phenylprop-1-amine (119356-76-2)

Conditions	Yield
With palladium 10% on activated carbon; acetic acid In methanol	98.2%

α-naphthol (90-15-3) + 3-chloropropiophenone (936-59-4) → N,N-dimethylamino-3-(naphthyl-1-oxy)-1-phenylprop-1-amine (119356-76-2)

Conditions	Yield
With sodium hydroxide In N,N-dimethyl-formamide at 60 - 65℃; for 5h; Reagent/catalyst; Temperature;	97.7%

C21H22ClNO (119357-32-3) → N,N-dimethylamino-3-(naphthyl-1-oxy)-1-phenylprop-1-amine (119356-76-2)

Conditions	Yield
With palladium 10% on activated carbon; acetic acid In methanol	94.2%

3-(naphthalen-1-yloxy)-1-phenylpropan-1-one (41198-42-9) + dimethyl amine (124-40-3) → N,N-dimethylamino-3-(naphthyl-1-oxy)-1-phenylprop-1-amine (119356-76-2)

Conditions	Yield
With formic acid at 170 - 180℃; for 18h; Time;	88.5%

C20H20O4S (1445281-20-8) + dimethyl amine (124-40-3) → N,N-dimethylamino-3-(naphthyl-1-oxy)-1-phenylprop-1-amine (119356-76-2)

Conditions	Yield
With potassium hydroxide In tetrahydrofuran at 0 - 35℃; for 40h;

3-(naphthalen-1-yloxy)-1-phenyl-propan-1-ol + dimethyl amine (124-40-3) → N,N-dimethylamino-3-(naphthyl-1-oxy)-1-phenylprop-1-amine (119356-76-2)

Conditions	Yield
Stage #1: 3-(naphthalen-1-yloxy)-1-phenyl-propan-1-ol With dmap; methanesulfonyl chloride; triethylamine In tetrahydrofuran at -5 - 0℃; Stage #2: dimethyl amine In tetrahydrofuran at 0 - 20℃; for 40h; Stage #3: With sodium hydroxide In tetrahydrofuran; water for 9 - 10h;

3-Amino-3-phenylpropionic acid (3646-50-2) → N,N-dimethylamino-3-(naphthyl-1-oxy)-1-phenylprop-1-amine (119356-76-2)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: sodium tetrahydroborate; iodine / tetrahydrofuran / 18 h / 66 °C 2.1: 8 h / 95 °C 3.1: sodium hydride / N,N-dimethyl-formamide / 1.5 h / 50 °C / Inert atmosphere 3.2: 6 h / 100 °C View Scheme
Multi-step reaction with 3 steps 1.1: sodium tetrahydroborate / tetrahydrofuran / 0.17 h / Cooling with ice 1.2: 7.5 h / 10 - 65 °C 2.1: water / 10 h / 90 °C / Cooling with ice 3.1: sodium hydride / N,N-dimethyl-formamide / 1 h / 60 °C / Cooling with ice 3.2: 9 h / 100 °C View Scheme

1-Fluoronaphthalene (321-38-0) + 3-(dimethylamino)-3-phenylpropan-1-ol (81402-52-0) → N,N-dimethylamino-3-(naphthyl-1-oxy)-1-phenylprop-1-amine (119356-76-2)

Conditions	Yield
Stage #1: 3-(dimethylamino)-3-phenylpropan-1-ol With sodium hydride In N,N-dimethyl-formamide at 50℃; for 1.5h; Inert atmosphere; Stage #2: 1-Fluoronaphthalene In N,N-dimethyl-formamide at 100℃; for 6h;	38.6 g
Stage #1: 3-(dimethylamino)-3-phenylpropan-1-ol With sodium hydride In N,N-dimethyl-formamide at 60℃; for 1h; Cooling with ice; Stage #2: 1-Fluoronaphthalene In N,N-dimethyl-formamide at 100℃; for 9h;

benzaldehyde (100-52-7) → N,N-dimethylamino-3-(naphthyl-1-oxy)-1-phenylprop-1-amine (119356-76-2)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: ammonium acetate / ethanol / 8 h / 80 °C 2.1: sodium tetrahydroborate; iodine / tetrahydrofuran / 18 h / 66 °C 3.1: 8 h / 95 °C 4.1: sodium hydride / N,N-dimethyl-formamide / 1.5 h / 50 °C / Inert atmosphere 4.2: 6 h / 100 °C View Scheme
Multi-step reaction with 4 steps 1.1: ammonium acetate / ethanol / 6 h / 78 °C 2.1: sodium tetrahydroborate / tetrahydrofuran / 0.17 h / Cooling with ice 2.2: 7.5 h / 10 - 65 °C 3.1: water / 10 h / 90 °C / Cooling with ice 4.1: sodium hydride / N,N-dimethyl-formamide / 1 h / 60 °C / Cooling with ice 4.2: 9 h / 100 °C View Scheme

3-amino-3-phenyl-1-propanol (14593-04-5, 82769-76-4) → N,N-dimethylamino-3-(naphthyl-1-oxy)-1-phenylprop-1-amine (119356-76-2)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: 8 h / 95 °C 2.1: sodium hydride / N,N-dimethyl-formamide / 1.5 h / 50 °C / Inert atmosphere 2.2: 6 h / 100 °C View Scheme
Multi-step reaction with 2 steps 1.1: water / 10 h / 90 °C / Cooling with ice 2.1: sodium hydride / N,N-dimethyl-formamide / 1 h / 60 °C / Cooling with ice 2.2: 9 h / 100 °C View Scheme

formaldehyd (50-00-0) + 1-phenyl-3-(naphthyl-1-oxy)propylamine (119357-34-5) → N,N-dimethylamino-3-(naphthyl-1-oxy)-1-phenylprop-1-amine (119356-76-2)

Conditions	Yield
With formic acid In water at 90℃; for 6h;

1-phenyl-3-naphthalenyloxypropane → N,N-dimethylamino-3-(naphthyl-1-oxy)-1-phenylprop-1-amine (119356-76-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: dibenzoyl peroxide; N-Bromosuccinimide / tetrachloromethane / 5 h / Irradiation; Reflux 2: acetone / 5 h / 50 °C / Cooling with ice 3: acetic acid; palladium 10% on activated carbon / methanol View Scheme
Multi-step reaction with 3 steps 1: dibenzoyl peroxide; N-chloro-succinimide / tetrachloromethane / 5 h / Reflux; Irradiation 2: acetone / 6 h / 50 °C / Cooling with ice 3: acetic acid; palladium 10% on activated carbon / methanol View Scheme

1-bromo-4-(3-bromo-3-phenylpropoxy)naphthalene → N,N-dimethylamino-3-(naphthyl-1-oxy)-1-phenylprop-1-amine (119356-76-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: acetone / 5 h / 50 °C / Cooling with ice 2: acetic acid; palladium 10% on activated carbon / methanol View Scheme

1-chloro-4-(3-chloro-3-phenylpropoxy)naphthalene → N,N-dimethylamino-3-(naphthyl-1-oxy)-1-phenylprop-1-amine (119356-76-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: acetone / 6 h / 50 °C / Cooling with ice 2: acetic acid; palladium 10% on activated carbon / methanol View Scheme

N,N-dimethylamino-3-(naphthyl-1-oxy)-1-phenylprop-1-amine (119356-76-2) → N,N-dimethylamino-3-(naphthyl-1-oxy)-1-phenylprop-1-amine hydrochloride

Conditions	Yield
With hydrogenchloride In ethyl acetate for 2h; pH=2; Cooling with ice;	85.8%

N,N-dimethylamino-3-(naphthyl-1-oxy)-1-phenylprop-1-amine (119356-76-2) + m → N,N-dimethylamino-3-(naphthyl-1-oxy)-1-phenylprop-1-amine hydrochloride

Conditions	Yield
With hydrogenchloride In ethanol pH=2 - 3; pH-value;	84.8%

N,N-dimethylamino-3-(naphthyl-1-oxy)-1-phenylprop-1-amine (119356-76-2) → Dapoxetine hydrochloride

Conditions	Yield
With hydrogenchloride; (1S)-10-camphorsulfonic acid In ethanol; water at 20℃; for 15h; Temperature; Solvent; Reagent/catalyst;	76%
Multi-step reaction with 3 steps 1: ethanol; water 2: sodium hydroxide / pH >= 13 3: hydrogenchloride / acetone View Scheme

N,N-dimethylamino-3-(naphthyl-1-oxy)-1-phenylprop-1-amine (119356-76-2) → dapoxetine

Conditions	Yield
With L-Tartaric acid In ethanol; water at 20℃; Cooling with ice;	37%
Multi-step reaction with 2 steps 1: ethanol; water 2: sodium hydroxide / pH >= 13 View Scheme

N,N-dimethylamino-3-(naphthyl-1-oxy)-1-phenylprop-1-amine (119356-76-2) + (2S,3S)-di-4-toluoyltartaric acid (32634-68-7) → dapoxetine DTTA salt

Conditions	Yield
In dichloromethane at 25 - 35℃; for 0.5h;

N,N-dimethylamino-3-(naphthyl-1-oxy)-1-phenylprop-1-amine (119356-76-2) + ammonium bromocamphorsulfonate (74165-69-8) → (+)-N,N-Dimethyl-1-phenyl-3-(1-naphthalenyloxy) propanamine (+)-3-bromocamphor-8-sulfonate

Conditions	Yield
In methanol; ethyl acetate

N,N-dimethylamino-3-(naphthyl-1-oxy)-1-phenylprop-1-amine (119356-76-2) + D-tartaric acid (147-71-7) → S-(+)-N,N-dimethyl-3-(naphthalen-1-yloxy)-1-phenylpropan-1-amine tartrate (1448512-87-5)

Conditions	Yield
In ethanol; water	3.5 g

Upstream product

• 119357-32-3 C₂₁H₂₂ClNO 
• 50-00-0 formaldehyd 
• 119357-34-5 1-phenyl-3-(naphthyl-1-oxy)propylamine 
• 14593-04-5 3-amino-3-phenyl-1-propanol 
• 100-52-7 benzaldehyde 
• 321-38-0 1-Fluoronaphthalene 
• 81402-52-0 3-(dimethylamino)-3-phenylpropan-1-ol 
• 3646-50-2 3-Amino-3-phenylpropionic acid 
• 908291-72-5 3-(naphthalen-1-yloxy)-1-phenyl-propan-1-ol 
• 124-40-3 dimethyl amine 
• 41198-42-9 3-(naphthalen-1-yloxy)-1-phenylpropan-1-one 
• 90-15-3 α-naphthol 
• 936-59-4 3-chloropropiophenone 
• 1445281-20-8 C₂₀H₂₀O₄S 

Downstream Products

• 1071929-03-7 Dapoxetine hydrochloride 
• 119356-77-3 dapoxetine 
• 1071929-03-7 N,N-dimethylamino-3-(naphthyl-1-oxy)-1-phenylprop-1-amine hydrochloride 

Relevant articles and documents

Development of novel triazole based dendrimer supported spiroborate chiral catalysts for the reduction of (: E)-O-benzyl oxime: An enantioselective synthesis of (S)-dapoxetine

Novel dendrimer supported spiroborate catalysts 2 and 3 have been synthesized using a click reaction as a key step. The catalytic efficiency of the catalysts have been verified with reduction of (E)-O-benzyl oxime 13 as a model substrate. Catalyst 3 was found to be better than catalyst 2 as the chemical yield and enantiomeric excess were significantly high with the former catalyst. Thus, catalyst 3 has been successfully used in the efficient synthesis of (S)-dapoxetine 14 with 94% ee and 46% overall yield in three steps. These catalysts could be easily recovered from the reaction solution by the solvent precipitation technique and could be reused five times without significant loss of activity and enantioselectivity.

Synthesis, separation-purification, and salt forming method of dapoxetine

The invention provides a novel synthesis, gradient separation-purification, and salt forming method of dapoxetine. Easily available and cheap benzaldehyde is taken as the primary raw material of the synthesis route. The whole reaction conditions are mild. The synthesis route is short. No highly toxic or explosive raw material is used. The problem of chiral separation is well solved in the route. During the separation process, the product is purified. Finally, chlorinated hydromethyl tert-butyl ether which does not have any side or toxic effect is used to carry out salt forming. A large amount of labor, material, and time is saved. The production cost is reduced. The synthesis does not need any special equipment. The operation is simple and convenient. The method has a good industrial application prospect.

A S - west reaches anchors the sandbank and its salt synthesis method

The invention discloses a synthetic method for S-dapoxetine. The synthetic method comprises the following steps: (1) resolving 1-phenyl-3-(naphthyl-1-oxy)propylamine for at least once with a resolving agent to obtain a resolved mixed system; (2) separating the resolved mixed system to obtain S-1-phenyl-3-(naphthyl-1-oxy)propylamine, and recycling mother liquor; (3) performing methylation on the S-1-phenyl-3-(naphthyl-1-oxy)propylamine to obtain S-dapoxetine. Compared with the conventional industrial production method, residual intermediate (R)-phenyl-3-(naphthyl-1-oxy)propylamine in the resolved mother liquor is firstly recycled on the basis of the prior art, then resolved again through D-(-) tartaric acid after racemization, and recycled, so that the yield is increased, the product waste is avoided, and the economic benefits are improved.