ChemicalBook CAS DataBase List 2-CHLORO-5-NITRO-3-(TRIFLUOROMETHYL)PYRIDINE

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

8synthesis methods

Product Name:2-CHLORO-5-NITRO-3-(TRIFLUOROMETHYL)PYRIDINE
CAS Number:99368-67-9
Molecular formula:C6H2ClF3N2O2
Molecular Weight:226.54

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

99368-66-8

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

99368-67-9

General procedure for the synthesis of 2-chloro-3-trifluoromethyl-5-nitropyridine from 2-hydroxy-5-nitro-3-trifluoromethylpyridine: Thionyl chloride (SOCl2, 18.45 mL, 253 mmol) was slowly added dropwise to a reaction vial containing 5-nitro-3-(trifluoromethyl)pyridin-2-ol (2.63 g, 12.64 mmol). Subsequently, N,N-dimethylformamide (DMF, 1.957 mL, 25.3 mmol) was added as a catalyst. The reaction mixture was stirred at 100°C for 10 hours. Upon completion of the reaction, the reaction solution was concentrated under reduced pressure to remove excess thionyl chloride. The concentrated residue was extracted by partitioning between ethyl acetate (EA) and saturated sodium bicarbonate (NaHCO3) solution. The organic phases were combined, washed with saturated brine, dried over anhydrous magnesium sulfate (MgSO4), filtered and concentrated under reduced pressure to afford the crude product 2-chloro-5-nitro-3-(trifluoromethyl)pyridine (2.46 g, 10.86 mmol, 86% yield), which could be used in the next reaction without further purification. Thin layer chromatography (TLC) analysis conditions: petroleum ether/ethyl acetate (PE/EA = 5:1), Rf = 0.6. 1H NMR (400 MHz, CDCl3) δ: 9.23-9.59 (m, 1H), 8.79 (d, J = 2.4 Hz, 1H).

99368-66-8
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99368-67-9
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Yield:99368-67-9 86%

Reaction Conditions:

with thionyl chloride in N,N-dimethyl-formamide at 100; for 10 h;Temperature;

Steps:

8.2 2-Chloro-5-nitro-3-(trifluoromethyl)pyridine
SOCl₂ (18.45 mL, 253 mmol) was added to a solution of 5-nitro-3-(trifluoromethyl)pyridin-2-ol (2.63 g, 12.64 mmol). DMF (1.957 mL, 25.3 mmol) was added and the mixture was at 100° C. for 10 h. Then the solution was concentrated and distributed between EA and saturated NaHCO₃ solution. The combined organic extract was washed with brine, dried over MgSO₄, filtered and concentrated. The resulting 2-chloro-5-nitro-3-(trifluoromethyl)pyridine (2.46 g, 10.86 mmol, 86% yield) was used in the next step without further purification. TLC (PE/EA=5:1, R_f=0.6): ¹H NMR (400 MHz, CDCl₃) δ: 9.23-9.59 (m, 1H), 8.79 (d, J=2.4 Hz, 1H).

References:

GlaxoSmithKline Intellectual Property Development Limited;EIDAM, Hilary Schenck;Raha, Kaushik;Gong, Zhen;Guan, Huiping;Wu, Chengde;Yang, Haiying;Yu, Haiyu;Zhang, Zhiliu;CHEUNG, Mui US2014/275111, 2014, A1 Location in patent:Paragraph 0259; 0260

FullText

680-15-9 Synthesis