104224-63-7

Basic information

• Product Name: 1-(5-Bromo-2-methoxy-phenyl)adamantane
• Synonyms: TRICYCLO[3.3.1.13,7]DECANE, 1-(5-BROMO-2-METHOXYPHENYL)-;1-(5-Bromo-2-methoxyphenyl)-tricyclo[3.3.1.13,7]decane;1-(5-bromo-2-methoxy-phenyl)adamantane;2-(1-ADAMANTYL)-4-BROMOANISOLE;2-(1-ADAMANTANE)-4-BROMOANISOLE;2-(Adamantan-1-yl)-4-bromoanisole, 2-(Adamantan-1-yl)-4-bromo-1-methoxybenzene;1-(5-BROMO-2-METHOXYPHENYL)TRYCYCLO[3,3,1,13,7]DECANE;1-(5-bromo-2-methoxyphenyl)-tricyclo[3,3,1,13,7]decane (intermediate of adapalene)
• CAS NO: 104224-63-7
• Molecular Formula: C₁₇H₂₁BrO
• Molecular Weight: 321.25
• EINECS: 1806241-263-5
• Product Categories: blocks;Bromides;APIs Intermediate;Adamantane derivatives;ADAPALENE;(intermediate of adapalene);Intermediates of Adapalene;API;Aromatics;Intermediates & Fine Chemicals;Metabolites & Impurities;Pharmaceuticals
• Mol File: 104224-63-7.mol
• Article Data: 14

Chemical Properties

• Melting Point: 139-141°C
• Boiling Point: 402.492 °C at 760 mmHg
• Flash Point: 160.342 °C
• Appearance: /
• Density: 1.346 g/cm³
• Vapor Pressure: 2.54E-06mmHg at 25°C
• Refractive Index: 1.593
• Storage Temp.: Refrigerator
• Solubility: Chloroform (Slightly), Ethyl Acetate (Slightly)
• CAS DataBase Reference: 1-(5-Bromo-2-methoxy-phenyl)adamantane(CAS DataBase Reference)
• NIST Chemistry Reference: 1-(5-Bromo-2-methoxy-phenyl)adamantane(104224-63-7)
• EPA Substance Registry System: 1-(5-Bromo-2-methoxy-phenyl)adamantane(104224-63-7)

Safety Data

• Hazard Codes: Xi
• Hazardous Substances Data: 104224-63-7(Hazardous Substances Data)

Usage

Chemical Properties

White Solid

Uses

Adapalene (A225000) impurity.

InChI:InChI=1/C17H21BrO/c1-19-16-3-2-14(18)7-15(16)17-8-11-4-12(9-17)6-13(5-11)10-17/h2-3,7,11-13H,4-6,8-10H2,1H3

Upstream product

• 77-78-1 dimethyl sulfate 
• 104224-68-2 2-(1-adamantyl)-4-bromophenol 
• 106-41-2 4-bromo-phenol 
• 104-92-7 1-bromo-4-methoxy-benzene 
• 768-95-6 1-adamanthanol 
• 74-88-4 methyl iodide 

Downstream Products

• 104224-62-6 3-(1-adamantyl)-4-methoxybenzoic acid 
• 106685-41-0 6-(3-adamantan-1-yl-4-methoxyphenyl)naphthalene-2-carboxylic acid methyl ester 
• 459423-32-6 3-(1-adamantyl)-4-methoxyphenylboronic acid 
• 142650-77-9 3-(1-adamantyl)-4-methoxyphenol 
• 107430-91-1 4-methoxy-3-tricyclo[3.3.1.1(0,0)]dec-1-yl benzaldehyde 
• 1036766-54-7 3-(1-adamantyl)-4-methoxybenzene magnesium bromide 
• 43109-77-9 1-(o-methoxyphenyl)adamantane 
• 1036406-09-3 C₂₄H₂₈O₂ 
• 1036766-56-9 2-(3-adamantan-1-yl-4-methoxyphenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane 
• 932033-57-3 3,3'-diadamantyl-4,4'-dimethoxybiphenyl 
• 104224-64-8 3-(1-adamantyl)-4-methoxybenzoic acid chloride 
• 142651-49-8 3-(1-Adamantyl)-4-methoxyphenylethanone 

Relevant articles and documents

A high yield and pilot-scale process for the preparation of adapalene

Strategies that were adopted during the process development of adapalene to achieve a cost-effective commercial-scale synthesis are described herein. These included (1) the use of AcOH/H2SO4 to afford 2-(1-adamantyl)-4-bromophenol in quantitative yield; (2) the dimethyl sulfate methylation to enhance the yield of methylation to 95%; (3) direct conversion of the Grignard reagent into methyl 6-(3-(1-adamantyl)-4-methoxyphenyl)-2- naphthoate by the catalysis of both PdCl2-(PPh3) 2 and ZnCl2 in high yield; (4) the use of EDTA-disodium salt dihydrate to ensure the heavy metal's content within acceptable limits; (5) the use of toluene to simplify the original Chromatographic purification to recrystallization. The pilot-scale synthesis of adapalene is described in detail in the Experimental Section.

Ion-exchange-resin-catalyzed adamantylation of phenol derivatives with adamantanols: Developing a clean process for synthesis of 2-(1-adamantyl)-4- bromophenol, A key intermediate of adapalene

A clean process has been developed for the synthesis of 2-adamantylphenol derivatives through adamantylation of substituted phenols with adamantanols catalyzed by commercially available and recyclable ion-exchange sulfonic acid resin in acetic acid.The sole byproduct of the adamantylation reaction,namely water,could be converted into the solvent acetic acid by addition of a slight excess of acetic anhydride during the work-up procedure,making the process waste-free except for regeneration of the ionexchange resin,and facilitating the recycling of the resin catalyst.The ion-exchange sulfonic acid resin catalyst could be readily recycled by filtration and directly reused at least ten times without a significant loss of activity.The key intermediate of adapalene,2-(1-adamantyl)-4-bromophenol,could be produced by means of this waste-free process.

METHOD FOR PREPARATION OF 6-[3(1-ADAMANTYL) -4-METHOXYPHENYL]-2-NAPHTOIC ACID

A method for preparation of 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid is disclosed based on “one pot” synthesis approach including a direct synthesis of boronic acid derivative from 2-(1-adamantyl)-4-bromoanisole and cycloboranes with a subsequent Suzuki-Miyaura coupling with 6-halonaphthenoates and basic hydrolysis of the reaction product in ethylene glycol or 1,2-propanediol.