Electric Literature of 103889-37-8, These common heterocyclic compound, 103889-37-8, name is 1-Chloro-3-fluoro-2-(trifluoromethyl)benzene, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.
To a mixture of l-chloro-3-fluoro-2-(trifluoromethyl)benzene (2 g, 10 mmol) in anhydrous tetrahydrofuran (40 mL) at -70 C under nitrogen was added dropwise 2 M lithium diisopropylamide (2.0 M in tetrahydrofuran/n-heptane, 7.6 mL, 15 mmol). The mixture was stirred for 1 hour, and then N, N-dimethylformamide (0.9 g, 12 mmol) was added dropwise at -70 C. The reaction was stirred at -70 C for another 1 hour, then quenched by addition of water (20 mL), acidified to pH 2 with concentrated hydrochloric acid at 0 C, and extracted with ethyl acetate (3 x 30 mL). The combined organic layers were washed with saturated brine (3 x 10 mL), dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give compound mixture B-185 (1.7 g, 11: 1 ratio of hydrate: aldehyde) as a yellow solid. -NMR (CD3OD, 400 MHz): delta 10.27 (s, 1H), 8.09-8.03 (m, 1H), 7.81 (t, J=8.0 Hz, 11H), 7.60 (d, J=8.0 Hz, 1H), 7.43 (d, J=8.8 Hz, 11H), 5.75 (s, 11H). To a solution of compound mixture B-185 (0.5 g, 2 mmol) in dichloromethane (5 mL) was added triethylamine (0.3 g, 3 mmol) and methyl 2-sulfanylacetate (0.3 g, 3 mmol). The mixture was stirred at 40 C for 20 hours, then diluted with water (40 mL) and extracted with ethyl acetate (3 chi 40 mL). The combined organic layers were washed with brine (3 x 10 mL), dried with anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel chromatography [petroleum ether: ethyl acetate = 10: 1] to give compound B-186 (0.4 g, 70% yield) as a white solid. -NMR (CD3OD, 400 MHz): delta 8.14 (d, J=6.4 Hz, 2H), 7.65 (d, J=8.4 Hz, 1H), 3.96 (s, 3H).
Statistics shows that 1-Chloro-3-fluoro-2-(trifluoromethyl)benzene is playing an increasingly important role. we look forward to future research findings about 103889-37-8.
Reference:
Patent; FORUM PHARMACEUTICALS, INC.; ACHARYA, Raksha; BURNETT, Duane, A.; BURSAVICH, Matthew, Gregory; COOK, Andrew, Simon; HARRISON, Bryce, Alden; KOENIG, Gerhard; MCRINER, Andrew, J.; (400 pag.)WO2016/100184; (2016); A1;,
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