1847-63-8

Basic information

• Product Name: Nafoxidine
• Synonyms: NSC-70735;U-11100A;Nafoxiden;1-[2-[4-(3,4-dihydro-6-Methoxy-2-phenyl-1-naphthalenyl)phenoxy]ethyl]pyrrolidine Hydrochloride;1-[2-[p-(3,4-dihydro-6-Methoxy-2-phenyl-1-naphthyl)phenoxy]ethyl]pyrrolidine Hydrochloride;11100A;CP-56;U 11100
• CAS NO: 1847-63-8
• Molecular Formula: C₂₉H₃₁NO₂*ClH
• Molecular Weight: 462.02288
• Mol File: 1847-63-8.mol
• Article Data: 6

Chemical Properties

• Melting Point: 165-168℃
• Boiling Point: 574.5°Cat760mmHg
• Flash Point: 176.7°C
• Appearance: white to tan/
• Density: 1.137g/cm³
• Vapor Pressure: 3.33E-13mmHg at 25°C
• Refractive Index: 1.608
• Storage Temp.: room temp
• Solubility: H2O: ≥8mg/mL
• CAS DataBase Reference: Nafoxidine(CAS DataBase Reference)
• NIST Chemistry Reference: Nafoxidine(1847-63-8)
• EPA Substance Registry System: Nafoxidine(1847-63-8)

Safety Data

• Hazard Codes: Xn
• Statements: 20/21/22-40
• Safety Statements: 22-36
• RIDADR: 2811
• WGK Germany: 3
• RTECS: UY0880000
• HazardClass: 6.1(b)
• PackingGroup: III
• Hazardous Substances Data: 1847-63-8(Hazardous Substances Data)

Usage

Chemical Properties

Off-White Solid

Uses

Nafoxidine is a non-steroidal antiestrogenic drug that is structurally related to Tamoxifen (T006000). Nafoxidine is a potent estrogen receptor antagonist that exhibits anti-proliferative properties.

InChI:InChI=1/C29H31NO2/c1-31-26-14-16-28-24(21-26)11-15-27(22-7-3-2-4-8-22)29(28)23-9-12-25(13-10-23)32-20-19-30-17-5-6-18-30/h2-4,7-10,12-14,16,21H,5-6,11,15,17-20H2,1H3

Upstream product

• 180915-95-1 1-{2-[4-(2-Bromo-6-methoxy-3,4-dihydronaphthalen-1-yl)phenoxy] ethyl}pyrrolidine 
• 497-19-8 sodium carbonate 
• 98-80-6 phenylboronic acid 
• 1081-73-8 1-[2-(4-bromophenoxy)ethyl]pyrrolidine 
• 1769-84-2 6-methoxy-2-phenyl-1-tetralone 
• 1845-11-0 nafoxidine 
• 123-75-1 pyrrolidine 
• 1449689-98-8 4-[4-(2-chloro-ethoxy)-phenyl]-7-methoxy-3-phenyl-1,2-dihydro-naphthalene 
• 1078-19-9 6-methoxy-3,4-dihydro-1(2H)-naphthalenone 
• 108-86-1 bromobenzene 

Downstream Products

• 5879-98-1 1-{2-[4-(6-methoxy-2-phenyl-1,2,3,4-tetrahydro-naphthalen-1-yl)-phenoxy]-ethyl}-pyrrolidine 
• 917591-23-2 1-{2-[4-(6-methoxy-2-phenyl-naphthalen-1-yl)-phenoxy]-ethyl}-pyrrolidine hydrochloride 
• 22845-53-0 cis-6-phenyl-5-[4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-2-methoxy-5,6,7,8-tetrahydronaphthalene hydrochloride 
• 180915-78-0 (5S,6R)-6-Phenyl-5-[4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-5,6,7,8-tetrahydro-naphthalen-2-ol 

Relevant articles and documents

Development of concise two-step catalytic approach towards lasofoxifene precursor nafoxidine

We have elaborated a two-step catalytic approach to nafoxidine, a key precursor to lasofoxifene. Firstly, an efficient α-arylation of 6-methoxy-3,4-dihydronaphthalen-1(2H)-one with chlorobenzene was developed, which operates at low 0.1 mol% Pd-132 catalyst loading in the presence of 1.9 equivalents of sodium tert-butoxide at 60 °C in 1,4-dioxane and provides 6-methoxy-2-phenyl-3,4-dihydronaphthalen-1(2H)-one in 90% yield. Secondly, we have demonstrated that 6-methoxy-2-phenyl-3,4-dihydronaphthalen-1(2H)-one can be converted to nafoxidine in 61% yield via CeCl3 promoted reaction with (4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)lithium, which is formed in-situ from the corresponding arylbromide precursor and n-butyllithium. Altogether, the shortest two-step approach to nafoxidine from simple tetralone commodity starting material has been developed with overall 55% yield. The developed synthetic approach to nafoxidine has several beneficial aspects over the one used in the synthetic route primarily developed for the preparation of lasofoxifene.

A new process for the synthesis of nafoxidene as a key intermediate of lasofoxifene

Abstract A novel brief process for the synthesis of nafoxidene has been developed. The epoxidation of 6-methoxy-1-{4-[2-(pyrrolin-1-yl)ethoxy)]phenyl}-3,4-dihydronaphthalene by m-CPBA directly gave the ketone 6-methoxy-1-[4-(2-(pyrrolidin-1-yl)ethoxy)phenyl]-3,4-dihydronaphthalen-2(1H)-one, which was subject to phenyl magnesium bromide/cerium chloride and subsequently treated with an acid to yield nafoxidene. In addition, the preparation of the starting naphthalene was also optimized by replacing the aromatic lithium at low temperature with its Grignard reagent at refluxing THF. This mild process, without the use of toxic or noble metals, was more cost-efficient and easily worked up.

Pharmaceutical composition and methods comprising combinations of 2-alkylidene-19-nor-vitamin D derivatives and an estrogen agonist/antagonist

The present invention relates to pharmaceutical compositions and methods of treatment comprising administering to a patient in need thereof a combination of a 2-alkylidene-19-nor-vitamin D derivative and an estrogen agonistlantagonist or a pharmaceuticall