59443-15-1

Basic information

• Product Name: 3'-BROMO-5'-CHLORO-2'-HYDROXYACETOPHENONE
• Synonyms: 3'-BROMO-5'-CHLORO-2'-HYDROXYACETOPHENONE;5-CHLORO-3-BROMO-2-HYDROXYACETOPHENONE;AKOS BB-6936;2-ACETYL-6-BROMO-4-CHLOROPHENOL;1-(3-Bromo-5-chloro-2-hydroxyphenyl)ethan-1-one;5-CHLORO-3-BROMO-2-HYDROXYACETOPHENONE,97 %;1-(3-bromo-5-chloro-2-hydroxyphenyl)ethanone;1-(3-bromo-5-chloro-2-hydroxyphenyl)ethanone, 5-Chloro-3-bromo-2-hydroxyacetophenone
• CAS NO: 59443-15-1
• Molecular Formula: C₈H₆BrClO₂
• Molecular Weight: 249.49
• Product Categories: Aromatic Acetophenones & Derivatives (substituted)
• Mol File: 59443-15-1.mol
• Article Data: 4

Chemical Properties

• Melting Point: 100-103 °C(lit.)
• Boiling Point: 297.8 °C at 760 mmHg
• Flash Point: 133.9 °C
• Appearance: /
• Density: 1.691 g/cm³
• Vapor Pressure: 0.000747mmHg at 25°C
• Refractive Index: 1.604
• Storage Temp.: 2-8°C
• PKA: 8.19±0.23(Predicted)
• CAS DataBase Reference: 3'-BROMO-5'-CHLORO-2'-HYDROXYACETOPHENONE(CAS DataBase Reference)
• NIST Chemistry Reference: 3'-BROMO-5'-CHLORO-2'-HYDROXYACETOPHENONE(59443-15-1)
• EPA Substance Registry System: 3'-BROMO-5'-CHLORO-2'-HYDROXYACETOPHENONE(59443-15-1)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36
• WGK Germany: 3
• Hazardous Substances Data: 59443-15-1(Hazardous Substances Data)

Usage

Preparation

Preparation by bromination of 5-chloro-2-hydroxyacetophenone in acetic acid (65%).

General Description

3′-Bromo-5′-chloro-2′-hydroxyacetophenone is a halogenated aromatic hydroxyl ketone. It participates in the synthesis of racemates of 8-bromo-6-chloro-2-alkyl substituted chroman-4-ones.

InChI:InChI=1/C8H6BrClO2/c1-4(11)6-2-5(10)3-7(9)8(6)12/h2-3,12H,1H3

Upstream product

• 1450-74-4 5-chloro-2-hydroxyacetophenone 
• 695-96-5 2-bromo-4-chlorophenol 
• 98434-18-5 2-bromo-4-chlorophenyl acetate 

Downstream Products

• 78095-38-2 (E)-1-(3-Bromo-5-chloro-2-hydroxy-phenyl)-3-furan-2-yl-propenone 
• 129632-22-0 (E)-3-Furan-2-yl-acrylic acid 2-acetyl-6-bromo-4-chloro-phenyl ester 
• 106551-39-7 2-Chloro-benzoic acid 2-acetyl-6-bromo-4-chloro-phenyl ester 
• 1210038-73-5 3'-bromo-2'-(2-bromoethoxy)-5'-chloroacetophenone 
• 1621457-77-9 2-acetyl-6-bromo-4-chlorophenyl 3-methoxy-2-nitrobenzoate 
• 1279711-24-8 C₁₈H₁₇BrCl₂N₄O₂ 
• 1279711-16-8 C₂₂H₁₉BrCl₂N₄O 
• 1279711-08-8 C₁₆H₁₅BrCl₂N₄O 
• 1392284-04-6 1,3-dibenzyl-7-bromo-9-chloro-4-(2-(1-tosyl-1H-indol-3-yl)ethyl)-2,3,4,5-tetrahydro-1H-chromeno[4,3-d]pyrimidine 

Relevant articles and documents

ROR-GAMMA INHIBITORS

The present invention relates to compounds of formula I and pharmaceutical compositions comprising compounds of formula I. Compounds of Formula I are useful in treatment of inflammatory, metabolic or autoimmune diseases which are mediated by RORy.

Pilot Plant Preparation of an αvβ3 Integrin Antagonist. Part 1. Process Research and Development of a (S)-β-Amino Acid Ester Intermediate: Synthesis via a Scalable, Diastereoselective Imino-Reformatsky Reaction

Described are four process research investigations directed toward discerning a scalable, enantioselective method for preparing (S)-β-amino acid ester 3, a key intermediate to the αvβ3 integrin antagonist 1. Reported are an asymmetric Michael reaction approach, attempts to enantioselectively hydrogenate an enamine, resolution of (±)-3 via diastereomeric salt formation, and a synthetic route employing a novel, diastereoselective imino-Reformatsky reaction. This last research initiative proved successful and was employed as the enabling route to initial API supply. Process development of this enabling chemistry is reported. The technical issues researched and optimized were (1) the necessity of employing MEM-protection for high yield and diastereoselectivity in the imino-Reformatsky reaction, (2) the reaction kinetics of MEM chloride hydrolysis and the application of these data to an on-scale quench procedure, (3) the efficient formation of the (S)-phenylglycinol imine 15 in NMP and a dehydration of this product solution on-scale, employing molecular sieves, (4) a calorimetric study of the Reformatsky reaction and the application of these data, (5) the replacement of Pb(OAc)4 with NaIO4 and the use of methylamine to sequester competing oxazolidine formation, and (6) further development of the isolation and purification protocol for the ethyl ester, p-TsOH salt of (S)-3. The results and challenges associated with two campaigns in which the potential commercial process was practiced are discussed.