2-CHLORO-5-NITRO-3-(TRIFLUOROMETHYL)PYRIDINE

SOClSOCReference Example 118 2-chloro-5-nitro-3-(trifluoromethyl)pyridine; A mixture of 5-nitro-3-(trifluoromethyl)pyridin-2-ol (2.65 g), phosphorus pentachloride (3.17 g) and phosphorus oxychloride (1.5 mL) was stirred at 90° C. for 3 hr. After cooling to room temperature, the reaction mixture was poured into ice, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=19:1-->3:1) to give the title compound as a yellow oil (yield 2.21 g, 77percent). To a mixture of 5-nitro-3- (trifluoromethyl) pyridin-2-ol (2 g 9.61 mmol) was added SOClB. 2-Chloro-5-nitro-3-(trifluoromethyl)pyridineIn a schlenck tube, a mixture of 2-chloro-3-iodo-5-nitropyridine (17.58 mmol, 5.00 g), methyl 2, 2-difluoro-2-(fluorosulfonyl)acetate (8.79 mmol, 1.12 ml) and CuI (2.64 mmol, 0.5 g) in DMF (30 ml) was heated at 7OIn a 100 mL round bottom flask, a mixture of 2-chloro-3-iodo-5-nitropyridine (250 mg, 0.88 mmol), methyl 2, 2-difluoro-2-(fluorosulfonyl)acetate (0.06 mL, 0.44 mmol) and Copper(l) iodide (25 mg, 0.13 mmol) in dimethylformamide was heated at 70 °C for 3h under hydrogen atmosphere. Another 0.03 mL methyl 2, 2-difluoro-2-(fluorosulfonyl)acetate was added and the mixture was heated at 70 °C for 16 h. The reaction mixture was cooled to room temperature, diluted with water and extracted with ethyl acetate. The organic layer was concentrated under reduced pressure to afford the crude which was purified by column chromatography to give 2-chloro-5-nitro-3-(trifluoromethyl)pyridine (41 mg, 21 percent).In a 100 mL round bottom flask, a mixture of 2-chloro-3-iodo-5-nitropyridine (250 mg, 0.88 mmol), methyl 2, 2-difluoro-2-(fluorosulfonyl)acetate (0.06 mL, 0.44 mmol) and Copper(l) iodide (25 mg, 0.13 mmol) in dimethylformamide was heated at 70 °C for 3 h under hydrogen atmosphere. Another 0.03 mL methyl 2, 2-difluoro-2-(fluorosulfonyl)acetate was added and the mixture was heated at 70 °C for 16 h. The reaction mixture was cooled to room temperature, diluted with water and extracted with ethyl acetate. The organic layer was concentrated under reduced pressure to afford the crude which was purified by column chromatography to give 2-chloro-5-nitro-3-(trifluoromethyl)pyridine (41 mg, 21 percent).Step 1: Step 1 a mixture of 5-nitro-3- (trifluoromethyl) pyridine -2 (1H) -One, 3 (1.50g, 7.21mmol), POClSynthesis of 2-chloro-5-nitro-3-(trifluoromethyl)pyridine, 4 (0076) (0077) A mixture of 5-nitro-3-(trifluoromethyl)pyridin-2(1H)-one 3 (1.50 g, 7.21 mmol), POClTo a stirred solution of diethylmalonate (5.0 g, 23.5 mmol) in THF (25 mL) was addedpotassium tert-butoxide (1M in THF, 70.5 mmol) at -10 °C and the mixture was stirred 10mm at the same temperature followed by 30 mm at RT. A solution of 2-chloro-S-nitro-3-(trifluoromethyl)pyridine (5.0 g, 23.52 mmol) in THF (25 mL) was added slowly to the mixture at 0 °C and the resultant mixture was stirred for 4-S h at RT. The mixture was quenched with aqueous ammonium chloride solution and extracted twice with ethyl acetate. The combined organic layers were washed with water followed by brine and dried over anhydrous sodium sulfate. The solution was filtered, concentrated to yield 5.1 g of the desired product. The crude amine was as such carried forward to the next step.

Molecular Weight:226.54
XLogP3:2.5
Hydrogen Bond Acceptor Count:6
Exact Mass:225.9756895
Monoisotopic Mass:225.9756895
Topological Polar Surface Area:58.7
Heavy Atom Count:14
Complexity:230
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes