4-broMo-2-(difluoroMethoxy)pyridine

Sodium chloro(difluoro)acetate (5.26 g, 34.5 mmol) and potassium carbonate (0568) (3.57 g, 25.8 mmol) were added to a solution of 4-bromopyridin-2(1 /-/)-one (3.00 g, 17.2 mmol) in /V, /V-dimethylformamide (30 mL), and the reaction mixture was stirred at 95 °C for 2 hours. Water (100 mL) was added, and the resulting mixture was extracted with ethyl acetate (3 x 50 mL). The combined organic layers were washed sequentially with water (200 mL) and with saturated aqueous sodium chloride solution (150 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. Silica gel chromatography (Eluent: 15: 1 petroleum ether / ethyl acetate) afforded the product as a pale yellow oil. Yield: 1 .5 g, 6.7 mmol, 39percent. Step 1. General procedure: 5-Bromo-2-tert-butylpyridine (500 mg; 2.34 mmol) is dissolved in 5 ml_ of dioxane. Copper iodide (89 mg, 0.47 mmol) is added and the mixture is placed under argon atmosphere. Sodium iodide is added and the mixture is stirred for a few minutes under argon atmosphere. N, N?-dimethylethylenediamine (100 mI_, 0.93 mmol) is added and the mixture is stirred at 130C over night. The mixture is allowed to cool to room temperature before being diluted with ethyl acetate and extracted with saturated aqueous solution of sodium bicarbonate twice. The organic layer is dried over magnesium sulfate, filtered and concentrated.Yield: 610 mg (95 % of theory)Mass spectrometry (ESI+): m/z = 262 [M+H]+HPLC (Method 3): Retention time = 1.176 min.To a suspension of 4-bromo-2-hydroxypyridine (3.0 g, 17.24 mmol) in Acetonitrile (35 mL) was added sodium chlorodifluoroacetate (3.15 g, 20.69 mmol). The reaction mixture was heated at 90 C over night. To the reaction mixture was added more CH3CN (35 ML), K2CO3 (3.57 g, 25.9 mmol) and sodium chlorodifluoroacetate (2 g). The reaction mixture was heated at 70 C over night. The reaction mixture was diluted with water and ethyl acetate. The organic layer was separated, washed with brine, dried over MgS04. The filtrate was concentrated in vacuo. The extract was purified via silica gel flash column chromatography, eluting with 0-25% ethyl acetate in hexane to give the latter came out peak as N-alkylated product and the first flushed out peak as Intermediate 30A (oil, 0.77 g, 3.44 mmol, 19.9% yield). LC-MS Anal. Calc'd for C6H4BrF2NO 222.94, found [M+H] 224, 226. Tr = 0.91 min (Method A). NMR (400MHz, chloroform-d) delta 8.05 (d, J=5.3 Hz, 1H), 7.67 - 7.29 (m, 1H), 7.29 - 7.27 (m, 1H), 7.13 (d, J=1.3 Hz, 1H).

Molecular Weight:224.00
XLogP3:2.8
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:2
Exact Mass:222.94443
Monoisotopic Mass:222.94443
Topological Polar Surface Area:22.1
Heavy Atom Count:11
Complexity:125
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes