2,6-Difluoropyridine-4-boronic acid

The third and final step for the production of 2, 6-difluoropyridin-4-ylboronic acid involves the lithiation of 2, 6-difluoro-4-hydrazinopyridine followed by addition of triisopropyl borate which can be depicted as follows: In the final step the reaction flask was charged with tetrahydrofuran (150 ml) and toluene(400 ml). Triisopropyl borate (47 g, 0.25 mol) and 4-bromo-2, 6-difluoropyridine (44 g, 0.22 mol) were introduced to the reaction vessel and the mixture was cooled to -75° C. under nitrogen atmosphere. n-BuLi (2.6 M solution in hexanes, 105 ml, 0.27 mol) was added dropwise through an addition funnel, keeping the temperature no higher than 70° C. during the addition process. Upon completion of addition stirring continued at -75° C. for 30 minutes and the cooling bath was removed, allowing the reaction mixture to warm up to -20° C. After quenching with 2 N hydrochloric acid (about 120 ml, to pH=2) and stirring for 30 minutes the organic phase was separated. The aqueous layer was extracted with 250 ml of ether two times. The combined organic phases were then washed with 500 ml of water, 250 ml of brine, dried over magnesium sulfate, stirred with activated charcoal for one hour, filtered through Celite and concentrated under reduced pressure. Hexanes (250 ml) were added to the residue to precipitate the solids. The flask was kept under refrigeration over night and the solids content was collected, rinsed with cold hexanes and dried. Since Under an argon atmosphere, in a 500 ml, three-neck flask, 5.00 g of To a mixture of degassed 1 , 4-dioxane (3.1 mL) and water (0.72 mL) in a microwave vial was added [1 , T-bis(diphenylphosphino)ferrocene]dichloropalladium(ll) complex with dichloromethane (0.006 g, 0.0072 mmol), followed by the title compound from Preparative Example B (0.07 g, 0.148 mmol), (2, 6-difluoropyridin-3-yl)boronic acid (0.028 g, 0.176 mmol) and cesium carbonate (0.096 g, 0.29 mmol). The reaction mixture was then heated at ~120C in a sand-bath for 6 hours. The reaction mixture was diluted with ethyl acetate (60 mL) and water (20 mL), the organic phase was separated, dried over Na2S04, filtered and the solvents were evaporated in vacuo. The dark residue was purified by chromatography on silica (25 g, puriFlash, Interchim) using a Biotage Isolera system employing an ethyl acetate/n-heptane gradient (5/95 -> 100/0 -> 100/0) to afford the title compound as an off- white solid (0.0606 g, 81 %). (0270) 1H-NMR (400 MHz, CDCI3) d = 9.29 (s, 1 H), 8.43 (d, 1 H), 8.27 (d, 1 H), 7.93 (d, 1 H), 7.60- 7.53 (m, 6H), 7.31-7.24 (m, 10H), 6.69 (dd, 1 H), 6.59 (d, 1 H) (0271) MS [M+H]+ = 525.26To a mixture of degassed 1 , 4-dioxane (3.1 mL) and water (0.72 mL) in a microwave vial was added [1 , T-bis(diphenylphosphino)ferrocene]dichloropalladium(ll) complex with dichloromethane (0.006 g, 0.0072 mmol), followed by the title compound from Preparative Example B (0.07 g, 0.148 mmol),

Molecular Weight:158.90
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:5
Rotatable Bond Count:1
Exact Mass:159.0303149
Monoisotopic Mass:159.0303149
Topological Polar Surface Area:53.4
Heavy Atom Count:11
Complexity:128
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes