- Tetramethylammonium Fluoride Alcohol Adducts for SNAr Fluorination
-
Nucleophilic aromatic fluorination (SNAr) is among the most common methods for the formation of C(sp2)-F bonds. Despite many recent advances, a long-standing limitation of these transformations is the requirement for rigorously dry, aprotic conditions to maintain the nucleophilicity of fluoride and suppress the generation of side products. This report addresses this challenge by leveraging tetramethylammonium fluoride alcohol adducts (Me4NF·ROH) as fluoride sources for SNAr fluorination. Through systematic tuning of the alcohol substituent (R), tetramethylammonium fluoride tert-amyl alcohol (Me4NF·t-AmylOH) was identified as an inexpensive, practical, and bench-stable reagent for SNAr fluorination under mild and convenient conditions (80 °C in DMSO, without the requirement for drying of reagents or solvent). A substrate scope of more than 50 (hetero) aryl halides and nitroarene electrophiles is demonstrated.
- Bland, Douglas C.,Lee, So Jeong,Morales-Colón, Mariá T.,Sanford, Melanie S.,Scott, Peter J. H.,See, Yi Yang
-
supporting information
p. 4493 - 4498
(2021/06/28)
-
- PROCESS FOR FLUORINATING COMPOUNDS
-
Disclosed are mild temperature (e.g., from 0 to 80°C) SNAr fluorinations of a variety of halide and sulfonate substituted aryl and heteroaryl substrates using NMe4F.
- -
-
Page/Page column 29; 33; 34
(2017/02/28)
-
- Anhydrous Tetramethylammonium Fluoride for Room-Temperature SNAr Fluorination
-
This paper describes the room-temperature SNAr fluorination of aryl halides and nitroarenes using anhydrous tetramethylammonium fluoride (NMe4F). This reagent effectively converts aryl-X (X = Cl, Br, I, NO2, OTf) to aryl-F under mild conditions (often room temperature). Substrates for this reaction include electron-deficient heteroaromatics (22 examples) and arenes (5 examples). The relative rates of the reactions vary with X as well as with the structure of the substrate. However, in general, substrates bearing X = NO2 or Br react fastest. In all cases examined, the yields of these reactions are comparable to or better than those obtained with CsF at elevated temperatures (i.e., more traditional halex fluorination conditions). The reactions also afford comparable yields on scales ranging from 100 mg to 10 g. A cost analysis is presented, which shows that fluorination with NMe4F is generally more cost-effective than fluorination with CsF.
- Schimler, Sydonie D.,Ryan, Sarah J.,Bland, Douglas C.,Anderson, John E.,Sanford, Melanie S.
-
p. 12137 - 12145
(2016/01/09)
-
- PTERIDINES AND THEIR USE AS AGROCHEMICALS
-
The present disclosure relates to 1- or 2-(4-(aryloxy)-phenyl)ethylamino-, oxy- or sulfanyl)pteridines and 1- or 2-(4-(heteroaryloxy)-phenyl)ethylamino-, oxy- or sulfanyl)pteridines and their use as agrochemicals and animal health products.
- -
-
Page/Page column 30
(2011/04/14)
-
- PTERIDINES AND THEIR USE AS AGROCHEMICALS
-
The present disclosure relates to 1- or 2-(4-(aryloxy)-phenyl)ethylamino-, oxy- or sulfanyl)pteridines and 1- or 2-(4-(heteroaryloxy)-phenyl)ethylamino-, oxy- or sulfanyl)pteridines and their use as agrochemicals and animal health products.
- -
-
Page/Page column 64
(2011/04/14)
-
- 5,8-DIFLUORO-4-(2-(4-(HETEROARYLOXY)-PHENYL)ETHYLAMINO)QUINAZOLINES AND THEIR USE AS AGROCHEMICALS
-
The present disclosure relates to 5,8-difluoro-4-(2-(4-(heteroaryloxy)-phenyl)ethylamino)quinazolines and their use as agrochemicals and animal health products.
- -
-
Page/Page column 50
(2010/04/06)
-
- Selective inhibitors of rock protein kinase and uses thereof
-
Described herein are compounds that are useful as ROCK inhibitors. These compounds, and pharmaceutically acceptable compositions thereof, are useful for treating or lessening the severity of a variety of disorders, including cardiovascular, inflammatory,
- -
-
Page/Page column 35
(2008/06/13)
-
- CB1 MODULATOR COMPOUNDS
-
Novel compounds of structural formula (I) are disclosed. As modulators of the Cannabinoid-1 (CB1) receptor, these compounds are useful in the treatment, prevention and suppression of diseases mediated by the CB1 receptor. As such, compounds of the present invention are useful as in the treatment, prevention and suppression of psychosis, memory deficits, cognitive disorders, migraine, neuropathy, neuro-inflammatory disorders (e.g., multiple sclerosis, Guillain-Barre syndrome and the inflammatory sequelae of viral encephalitis), cerebral vascular accidents, head trauma, anxiety disorders, stress, epilepsy, Parkinson's disease, and schizophrenia. The compounds are also useful for the treatment of substance abuse disorders, particularly to opiates, alcohol, and nicotine. The compounds are also useful for the treatment of obesity or eating disorders associated with excessive food intake and complications associated therewith.
- -
-
Page/Page column 60
(2008/06/13)
-
- Practical routes toward the synthesis of 2-halo- and 2-alkylamino-4-pyridinecarboxaldehydes
-
We recently required an efficient synthesis of 2-halo- and 2-alkylamino-4-pyridinecarboxaldehydes. Several routes to these compounds were investigated resulting in efficient and practical procedures from readily available and inexpensive starting materials.
- Frey, Lisa F,Marcantonio, Karen,Frantz, Doug E,Murry, Jerry A,Tillyer, Richard D,Grabowski, Edward J.J,Reider, Paul J
-
p. 6815 - 6818
(2007/10/03)
-