3-Chloro-2-fluoro-pyridine

General procedure: To a solution of 2, 3-dichloropyridine(1.00 g, 6.76 mmol) in DMSO (33.8 ml) was added CsF (2.053 g, 13.51mmol) at room temperature. The mixture was stirred at 110 °C under air for 20h. The mixture was quenched with water at room temperature and extracted withEtOAc. The organic layer was separated, washed with water and brine, dried overNaGeneral procedure: In Situ TBAF* with DS-2 [0087] It was found that pre-formation of TBAF* is not necessary to facilitate fluorination at room temperature. Weighing the substrate and TBACN into the reaction vessel followed by DMSO and the appropriate amount of C6F6 furnishes the desired product in excellent yield (Table 1). [TABLE-US-00001] TABLE 1 Fluorination of DS-2 with in situ generated anhydrous TBAF* Entry TBAF* Equiv Yield 1 2.0 >99% 2 2.0 >99% 3 4.0 >99% 4 4.0 >99% In addition to the model substrate DS-2, other chloropicolinates, as well as simple chloropyridines, underwent fluorination with the disclosed methods. 5-Chloropicolinates went to full conversion as demonstrated in Scheme 2 (top row). 5-Fluoropicolinic acid, however, was only formed in small quantities presumably due to deprotonation by fluoride thereby inactivating the substrate to nucleophilic aromatic substitution. Simpler chloropyridines were less effective as substrates for this method in accordance to the reactivity observed by DiMagno et al. 4, 5-Dichloro-6-arylpicolinates (Scheme 2, bottom row) demonstrated fluorination first at the more activated 4-position followed by fluorination of the less activated 5-position, although the total yield was diminished due to the production of the undesired bis-cyanopicolinate product. [0091]General procedure: General Procedure E: General Experimental Details for NMR Yields Reported in Figure 3. In a drybox, anhydrous NMe4F (18.6 mg, 0.2 jumol, 2 equiv) and the appropriate aryi chloride or nitroarene substrate (0.1 nimol, 1 equiv) were weighed into a 4 mL vial equipped with a micro stirbar. DMF (0.5 mL) was added, and the viai was removed from the drybox and stirred at room temperature unless otherwise noted for 24 hours. The reaction was cooled to room temperature and an internal standard (1, 3, 5-trifluorobenzene, 100 iL of a 0.5 M solution in toluene) was added. An aliquot was removed for analysis by 59F NMR spectroscopy and GCMS.In a 20 mL vial was dissolved 3-hydroxy-2, 2-dimethyl-/V-(l-methylpiperidin-4- yl)propanamide (0.138 g, 0.380 mmol) in DMF (1.5 mL) to give a colorless solution. Sodium hydride (60 wt %, 0.035 g, 0.87 mmol) was added. After stirring for 30 minutes at room temperature,

Molecular Weight:131.53
XLogP3:1.6
Hydrogen Bond Acceptor Count:2
Exact Mass:130.9938050
Monoisotopic Mass:130.9938050
Topological Polar Surface Area:12.9
Heavy Atom Count:8
Complexity:78.8
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes