496-69-5

Usage

Chemical Properties

light brown to brown crystalline solid

Uses

2-Bromo-4-fluorophenol was used in preparation of 4,4-difluoro-2-bromo-cyclohexadienone and 6-(aminomethylphenoxy)benzoxaborole analogs.

InChI:InChI=1/C15H16F3NO5/c1-3-22-13(20)10(14(21)23-4-2)9-19-11-7-5-6-8-12(11)24-15(16,17)18/h5-9,19H,3-4H2,1-2H3

Upstream product

• 371-41-5 4-Fluorophenol 
• 371-40-4 4-fluoroaniline 
• 452-08-4 2-bromo-4-fluoro-1-methoxybenzene 
• 2198-66-5 2-bromo-4-tert-butylphenol 
• 1019441-67-8 2-bromo-4-fluoro-1-((4-methoxybenzyl)oxy)benzene 
• 474711-11-0 2-bromo-4-fluoro-1-(methoxymethoxy)benzene 
• 400-31-7 1,1,1-trifluoro-4-methyl-pent-3-en-2-one 
• 202865-73-4 2-bromo-4-fluoro-1-iodobenzene 

Downstream Products

• 399-40-6 (2-bromo-4-fluoro-phenoxy)-acetic acid 
• 32862-06-9 C₁₃H₉BrFNO₄ 
• 32862-07-0 C₁₄H₁₁BrFNO₄ 
• 326-69-2 1-bromo-2-ethoxy-5-fluorobenzene 
• 190966-87-1 2-(2-Bromo-4-fluoro-phenoxy)-5-nitro-thiophene 
• 347-54-6 5-fluoro-2-hydroxybenzaldehyde 
• 1016497-01-0 2-(2-bromo-4-fluoro-phenoxy)-3-nitro-pyridine 
• 1026887-70-6 1-[4-(2-bromo-4-fluoro-phenoxy)-3-nitro-phenyl]-ethanone 
• 480439-44-9 1-acetoxy-2-bromo-4-fluorobenzene 
• 152520-56-4 d-nebivolol hydrochloride 
• 212909-78-9 2-propenyl-4-fluorophenol 
• 212909-91-6 tert-Butyl-{(1R,2S)-2-[4-fluoro-2-((Z)-propenyl)-phenoxy]-cyclohept-3-enyloxy}-dimethyl-silane 
• 212909-84-7 tert-Butyl-{(1R,2R)-2-[4-fluoro-2-((Z)-propenyl)-phenoxy]-cyclohept-3-enyloxy}-dimethyl-silane 
• 474711-11-0 2-bromo-4-fluoro-1-(methoxymethoxy)benzene 

Relevant academic research and scientific papers

Regioselective monobromination of phenols with KBr and ZnAl–BrO3?–layered double hydroxides

The regioselective mono-bromination of phenols has been successfully developed with KBr and ZnAl–BrO3?–layered double hydroxides (abbreviated as ZnAl–BrO3?–LDHs) as brominating reagents. The para site is much favorable and the ortho site takes the priority if para site is occupied. This reaction featured with excellent regioselectivity, cheap brominating reagents, mild reaction condition, high atom economy, broad substrate scope, and provided an efficient method to synthesize bromophenols.

Trifluoromethyl aryl sulfonates (TFMS): An applicable trifluoromethoxylation reagent

Fluorine is probably another favorite hetero-atom for incorporation into small molecules after nitrogen. Among many fluorine-containing groups, trifluoromethyl aryl ethers (ArOCF3) have unique properties in drug design and are difficult to be synthesized, and many different methods were developed to prepare them. A novel one-pot synthesis of o-iodine-aryl trifluoromethyl ethers (ArOCF3I) was described by the reaction of trifluoromethoxylation and iodination with trifluoromethyl aryl sulfonates (TFMS) in this manuscript. The reaction conditions were optimized by screening different solvents, crown ethers, substrates and the ratios and the yields of products were in moderate to high yields (up to 86%).

Photoinduced Synthesis of Dibenzofurans: Intramolecular and Intermolecular Comparative Methodologies

The SRN1 reaction has been used as a powerful tool for the synthesis of heterocycles, and only a few studies about photoinduced intramolecular cyclization to generate a new C-O bond by a radical pathway have been reported. This work introduces two strategies for the synthesis of substituted dibenzofurans by electron transfer (eT) reactions. The first one is a three-step process that comprises bromination of o-arylphenols, Suzuki-Miyaura cross-coupling and photoinduced cyclization in order to obtain the above-mentioned products. The second one is a metal-free procedure and does not require any photocatalyst. Different solvents were tested, and the yields ranged from low to moderate. A comparison was established between both methodologies, showing that the second one is the most suitable for the synthesis of dibenzofurans.

Bismuth trichloride–mediated cleavage of phenolic methoxymethyl ethers

A simple and efficient method for removal of phenolic methoxymethyl ethers in the presence of 30?mol% of bismuth trichloride in acetonitrile/water is described. Notable features of the cleavage protocol entail use of an ecofriendly bismuth reagent, ease of handling, low cost, operational simplicity, and good functional group compatibility. A number of structurally varied phenolic methoxymethyl ethers were cleaved in good to excellent yields.

Selective and efficient generation of ortho-brominated para-substituted phenols in ACS-grade methanol

The mono ortho-bromination of phenolic building blocks by NBS has been achieved in short reaction times (15-20 min) using ACS-grade methanol as a solvent. The reactions can be conducted on phenol, naphthol and biphenol substrates, giving yields of >86% on gram scale. Excellent selectivity for the desired mono ortho-brominated products is achieved in the presence of 10 mol % para-TsOH, and the reaction is shown to be tolerant of a range of substituents, including CH3/ F,and NHBoc.

A convenient approach for the deprotection and scavenging of the PMB group using POCl3

A convenient and high yielding approach for the deprotection and scavenging of the p-methoxybenzyl (PMB) group in PMB ethers and PMB esters was developed using POCl3 as the reagent. 4-Methoxybenzyl chloride, a starting material used for the preparation of PMB ethers and esters was regenerated in the deprotection step. This mild and selective procedure tolerates several acid sensitive functional groups. The Royal Society of Chemistry 2013.

Palladium-catalyzed asymmetric intermolecular cyclization

Domino cyclization: Alkylpalladium intermediates in an asymmetric Heck reaction were intercepted by a second alkene to give tricyclic products with high enantioselectivity (see scheme; Boc=tert-butoxycarbonyl). The method was applied to the asymmetric syn

Multisubstituted benzo[b]furans through a copper- and/or palladium-catalyzed assembly and functionalization process

Full details as well as the study of the scope, limitations, and further elaboration of a straightforward approach to the synthesis of 2,5,7-trisubstituted benzo[b]furans from 2-bromo- and 2-chloro-6-iodo-4- substituted phenols through a consecutive copper- and/or palladium-catalyzed assembly and functionalization process is described. Functionalization at the C(7) position is carried out by Suzuki-Miyaura cross-coupling, alkynylation, alkenylation, and C-N bond forming reactions. A one-pot protocol for the synthesis of 2,5,7-trisubstituted benzo[b]furans is also reported.

Development of a large scale asymmetric synthesis of the glucocorticoid agonist BI 653048 BS H3PO4

The development of a large scale synthesis of the glucocorticoid agonist BI 653048 BS H3PO4 (1·H3PO4) is presented. A key trifluoromethyl ketone intermediate 22 containing an N-(4-methoxyphenyl)ethyl amide was prepared by an enolization/bromine-magnesium exchange/electrophile trapping reaction. A nonselective propargylation of trifluoromethyl ketone 22 gave the desired diastereomer in 32% yield and with dr = 98:2 from a 1:1 diastereomeric mixture after crystallization. Subsequently, an asymmetric propargylation was developed which provided the desired diastereomer in 4:1 diastereoselectivity and 75% yield with dr = 99:1 after crystallization. The azaindole moiety was efficiently installed by a one-pot cross coupling/indolization reaction. An efficient deprotection of the 4-methoxyphenethyl group was developed using H3PO4/anisole to produce the anisole solvate of the API in high yield and purity. The final form, a phosphoric acid cocrystal, was produced in high yield and purity and with consistent control of particle size.

Metal-free oxidative fluorination of phenols with [18F]fluoride

The radiochemical synthesis of [18F]4-fluorophenols is based on phenol umpolung under oxidative conditions and direct nucleophilic fluorination with [18F]fluoride (see scheme, TBAF=tetra-n-butylammonium fluoride, TFA=trifluoroacetic acid). Readily available O-unprotected 4-tert-butyl phenols are used as precursors in this one-pot protocol. The reaction is completed in less than 30 minutes at room temperature and can be performed using standard or microfluidic technology. Copyright