Rapid microwave-assisted synthesis of phenyl ethers under mildly basic and nonaqueous conditions

Sarju, Julien; Danks, Timothy N.; Wagner, Gabriele

doi:10.1016/j.tetlet.2004.08.087

Cited by 20 publications

(9 citation statements)

References 24 publications

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“…( 24 ) Therefore, we prepared potassium (3,5-dimethylisoxazol-4-yl)trifluoroborate 8 from (3,5-dimethylisoxazol-4-yl)boronic acid. ( 24 ) Coupling of 8 to commercially available aryl bromides 5 and 6 , and aryl bromide 7 (easily prepared from 3-bromophenol,( 25 ) Supporting Information , Scheme S2) afforded 3,5-dimethyl-4-phenylisoxazole 3a and the 3′-substituted 3,5-dimethyl-4-phenylisoxazoles 3b and 3c in excellent yields (Scheme 1 ). Although the coupling reactions did proceed when conducted with (3,5-dimethylisoxazol-4-yl)boronic acid (data not shown), the yields observed were lower than those in the route described above.…”

Section: Resultsmentioning

confidence: 99%

3,5-Dimethylisoxazoles Act As Acetyl-lysine-mimetic Bromodomain Ligands

et al. 2011

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Histone–lysine acetylation is a vital chromatin post-translational modification involved in the epigenetic regulation of gene transcription. Bromodomains bind acetylated lysines, acting as readers of the histone-acetylation code. Competitive inhibitors of this interaction have antiproliferative and anti-inflammatory properties. With 57 distinct bromodomains known, the discovery of subtype-selective inhibitors of the histone–bromodomain interaction is of great importance. We have identified the 3,5-dimethylisoxazole moiety as a novel acetyl-lysine bioisostere, which displaces acetylated histone-mimicking peptides from bromodomains. Using X-ray crystallographic analysis, we have determined the interactions responsible for the activity and selectivity of 4-substituted 3,5-dimethylisoxazoles against a selection of phylogenetically diverse bromodomains. By exploiting these interactions, we have developed compound 4d, which has IC50 values of <5 μM for the bromodomain-containing proteins BRD2(1) and BRD4(1). These compounds are promising leads for the further development of selective probes for the bromodomain and extra C-terminal domain (BET) family and CREBBP bromodomains.

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Section: Resultsmentioning

confidence: 99%

3,5-Dimethylisoxazoles Act As Acetyl-lysine-mimetic Bromodomain Ligands

et al. 2011

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“…4-Nitrophenetol ( 6 ) and propoxybenzene ( 7 ) were synthesized via the Williamson ether synthesis from the corresponding phenols using bromoethane or 1-bromopropane, respectively (Scheme ). The employed method was adapted from a protocol where a biphasic system of K 2 CO 3 in MeOH was found to be effective . Equimolar amounts of the phenol and base (5 mmol) were reacted with 1.2 equiv of alkyl bromide in EtOH as solvent.…”

Section: Resultsmentioning

confidence: 99%

“…The employed method was adapted from a protocol where a biphasic system of K 2 CO 3 in MeOH was found to be effective. 18 Equimolar amounts of the phenol and base (5 mmol) were reacted with 1.2 equiv of alkyl bromide in EtOH as solvent. For the more volatile bromoethane (bp 38 °C), a temperature of 120 °C had to be selected in order not to exceed the pressure limit of the instruments (20 bar), whereas for 1-bromopropane (bp 71 °C), 140 °C was possible.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Design and Performance Validation of a Conductively Heated Sealed-Vessel Reactor for Organic Synthesis

et al. 2016

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A newly designed robust and safe laboratory scale reactor for syntheses under sealed-vessel conditions at 250 °C maximum temperature and 20 bar maximum pressure is presented. The reactor employs conductive heating of a sealed glass vessel via a stainless steel heating jacket and implements both online temperature and pressure monitoring in addition to magnetic stirring. Reactions are performed in 10 mL borosilicate vials that are sealed with a silicone cap and Teflon septum and allow syntheses to be performed on a 2-6 mL scale. This conductively heated reactor is compared to a standard single-mode sealed-vessel microwave instrument with respect to heating and cooling performance, stirring efficiency, and temperature and pressure control. Importantly, comparison of the reaction outcome for a number of different synthetic transformations performed side by side in the new device and a standard microwave reactor suggest that results obtained using microwave conditions can be readily mimicked in the operationally much simpler and smaller conventionally heated device.

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“…More recently, aryl alkyl ether synthesis has been adapted to the single-mode sealed-vessel microwave reactor. A biphasic system of potassium carbonate in methanol was found to be effective with phenols bearing an electron-withdrawing substituent in the paraposition and non-activated alkyl bromides and chlorides [5]. The current procedure was adapted from this methodology.…”

Section: Work-up and Isolationmentioning

confidence: 99%

Experimental Protocols

2008

Practical Microwave Synthesis for Organic Chemists

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Rapid microwave-assisted synthesis of phenyl ethers under mildly basic and nonaqueous conditions

Cited by 20 publications

References 24 publications

3,5-Dimethylisoxazoles Act As Acetyl-lysine-mimetic Bromodomain Ligands

3,5-Dimethylisoxazoles Act As Acetyl-lysine-mimetic Bromodomain Ligands

Design and Performance Validation of a Conductively Heated Sealed-Vessel Reactor for Organic Synthesis

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