Synthetic Route of 115309-57-4, With the rapid development and complex challenges of chemical substances, the synthesis of new drugs is usually one of the most effective ways to increase yield.115309-57-4, name is tert-Butyl 6-chloronicotinate, molecular formula is C10H12ClNO2, molecular weight is 213.6608, as common compound, the synthetic route is as follows.
General procedure: To 6-chloronicotinic acid 19a (10 g) in methylene chloride(100 ml) solution, N,N?-diisopropyl-O-tert-butylisourea (50 g) wasadded and the mixture was stirred under heating and reflux for16 h. The insoluble compound was filtered out, and the filtratewas concentrated. The residue was purified by silica gel column chromatography (chloroform/ethyl acetate = 6/1) to obtain the compound 20a (11.66 g). To the compound 20a (6.0 g) in dimethylacetoamide (30 ml) solution, tris(dibenzylideneacetone)dipalladium (0.51 g), zinc cyanide (0.22 g), diphenylphosphinoferrocene (0.62 g), and zinc powder (1.98 g) were added and the mixture was stirred under argon atmosphere at 120 C for 3 h. The reaction solution was filtered by sellite, which was then washed with ethyl acetate. Then, the filtrate was washed with distilled water and saturated saline, then the organic layer was dried over with anhydrous sodium sulfate and concentrated. The obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate= 5/1) to obtain the compound 21a (3.59 g). To copper(I) iodide(0.93 g) in tetrahydrofuran (50 ml) suspension, ethylmagnesium bromide (0.86 M tetrahydrofuran solution)(12.5 ml) was added dropwise under cooling at 0 C, the mixture was stirred at 0 C for 30 min, then the compound 21a (1.0 g) obtained above in tetrahydrofuran (10 ml) solution was added atthe 20 C. After stirring for 30 min at that temperature, 28% ammonia solution in water and ethyl acetate were added to the mixture and the solution separated. The aqueous layer was extracted with ethyl acetate, while the combined organic layer was washed with saturated saline, then was dried over with anhydrous sodium sulfate and concentrated. The obtained residue was purifiedby silica gel column chromatography (hexane/ethyl acetate= 8/1) to obtained the compound 22a (0.47 g). To the compound 22a (200 mg) in tetrahydrofuran (1 ml) solution, (-)-B-chlorodiisopinocampheylborane (65% hexane solution) (0.92 ml) was added dropwise under cooling at 20 C, then the mixture was stirred at that temperature for 18 h. Then, ether and distilled water were added to the reaction mixture, and the solution was separated. The organic layer was extracted with distilled water and 1 M hydrogen chloride. Then, the combined aqueous layer was neutralized by sodium hydrogen carbonate, and extracted with ethyl acetate. Organic layer was washed with saturated saline, then was dried over with anhydrous sodium sulfate and concentrated to obtained the title compound (150 mg, 84% ee). The optical purity was determined using CHIRALCEL AD-H(Daicel Chemical Industries) (movement phase: hexane/ethanol= 98/2, 1.0 ml/min).
Statistics shows that 115309-57-4 is playing an increasingly important role. we look forward to future research findings about tert-Butyl 6-chloronicotinate.
Reference:
Article; Tanaka, Taisaku; Sugawara, Hajime; Maruoka, Hiroshi; Imajo, Seiichi; Muto, Tsuyoshi; Bioorganic and Medicinal Chemistry; vol. 21; 14; (2013); p. 4233 – 4249;,
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