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A kind of preparation method of 2-chloro-5-ethylpyridine

A technology of ethylpyridine and vinylpyridine, applied in chemical instruments and methods, organic compound/hydride/coordination complex catalysts, organic chemistry, etc., can solve the problems of low yield and long steps of key ring-forming steps , to achieve the effect of convenient purification, high selectivity and high yield

Inactive Publication Date: 2017-04-12
SUZHOU SHIYA BIOPHARMLS
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  • Abstract
  • Description
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AI Technical Summary

Problems solved by technology

The method has long steps, the yield of the key ring-forming step is low, and the product still needs to be purified by fractional distillation

Method used

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  • A kind of preparation method of 2-chloro-5-ethylpyridine
  • A kind of preparation method of 2-chloro-5-ethylpyridine
  • A kind of preparation method of 2-chloro-5-ethylpyridine

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Embodiment 12

[0027] The preparation of embodiment 12-chloro-5-vinylpyridine (method 1)

[0028] In a 500ml pressure bottle, mix 2-chloro-5-bromopyridine (9.6g, 50mmol) and 4,4,5,5-tetramethyl-2-vinyl-1,3,2-dioxaborol Naphthene (10.0 g, 65 mmol) was added to ethylene glycol dimethyl ether (225 mL) and 2M aqueous sodium carbonate (75 mL) to form a two-phase mixed system. Under nitrogen atmosphere, tetrakis(triphenylphosphine)palladium(0) (2.9 g, 2.5 mmol) was added to the mixed system. Subsequently, the pressure bottle was sealed, and the reaction system was stirred at 84° C. for 16 hours. The reaction mixture was diluted with 150 mL of water and 150 mL of ethyl acetate, and the white solid was removed by filtration. After the two phases were separated, the aqueous phase was extracted with 40 ml of ethyl acetate, the combined organic phase was dried over anhydrous magnesium sulfate, filtered, concentrated by rotary evaporation to about 20 ml, and purified by column chromatography to obtain...

Embodiment 22

[0030] The preparation of embodiment 22-chloro-5-vinylpyridine (method 2)

[0031] Potassium tert-butoxide (28 g, 250 mmol) was added portionwise to a suspension of methyltriphenylphosphine bromide (107 g, 300 mmol) in anhydrous tetrahydrofuran (500 ml) at 0°C. After stirring for 0.5 hour, a solution of 2-chloro-5-formylpyridine (35.4 g, 250 mmol) in anhydrous tetrahydrofuran (200 ml) was slowly added dropwise to the reaction system. After the dropwise addition was complete, the reaction mixture was stirred at 0° C. for 1 hour. Subsequently, the ice bath was removed, and the reaction mixture was stirred at room temperature for 1.5 hours. Saturated ammonium chloride solution (750ml) and ethyl acetate (400ml) were added. After the two phases were separated, the aqueous phase was extracted with 100 ml of ethyl acetate, the combined organic phase was dried over anhydrous magnesium sulfate, filtered, concentrated by rotary evaporation to about 100 ml, and purified by column chrom...

Embodiment 32

[0032] The preparation of embodiment 32-chloro-5-ethylpyridine

[0033] 2-Chloro-5-vinylpyridine (1g, 7.2mmol) was dissolved in 20ml of methanol, and after the resulting solution was passed through hydrogen for 2 minutes, 1,5-cyclooctadiene (pyridine) (tricyclohexylphosphine) iridium (I ) hexafluorophosphate catalyst (0.1 g), and subsequently, the mixture was reacted in a hydrogenation reactor (1 atm of hydrogen) for 2 hours. After the reaction solution was filtered and concentrated through diatomaceous earth, 10ml of dichloromethane and 10ml of water were added. After the organic phase was separated, it was dried with anhydrous magnesium sulfate, filtered, and concentrated by rotary evaporation to obtain 0.84g of 2-chloro-5-ethylpyridine in the form of Pale yellow liquid, yield 83%. The purity detected by HPLC is greater than 98%.

[0034] MS(EI)m / z 142.3[MH] + ; 1 H-NMR (400MHz, CDCl 3 ) δppm: 8.23(d, 1H), 7.48(q, 1H), 7.25(t, 1H), 2.63(q, 2H), 1.25(t, 3H).

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Abstract

The present invention discloses a 2-chloro-5-ethyl pyridine synthesis method. According to the method, a Suzuki reaction is performed to convert 2-chloro-5-bromopyridine into 2-chloro-5-vinylpyridine, or a Wittig reaction is performed to convert 2-chloro-5-formyl pyridine into 2-chloro-5-vinylpyridine, and further an iridium-containing catalyst having a structure represented by a formula (I) is adopted to carry out selective hydrogenation to convert the 2-chloro-5-vinylpyridine into the 2-chloro-5-ethyl pyridine, wherein R is cyclohexyl, n-butyl or phenyl, and L is pyridine or unsaturated nitrogen-containing carbene. The method of the present invention has advantages of high selectivity, high yield and convenient purification. The formula (I) is defined in the instruction.

Description

technical field [0001] The invention belongs to the technical field of organic synthesis and relates to a synthesis method of 2-chloro-5-ethylpyridine. Background technique [0002] 2-Chloro-5-ethylpyridine (Formula 1) is an important pharmaceutical intermediate. In 1991, the German Bayer company disclosed in U.S. Patent US Pat.5010201A the use of phosphorus oxychloride, dichlorophosphate or dichlorophosphoramide to convert 3-methylpyridine-N-oxide into 2-chloro-5-methylpyridine Methods. In 1994, US Pat.5334724A extended the method to use benzoyl chloride, phthaloyl chloride or isophthaloyl chloride to synthesize 2-chloro-5-picoline. The synthetic route of this method is shown in formula 2, and its advantage is that productive rate is higher, and shortcoming is when obtaining 2-chloro-5-picoline, can generate by-product 2-chloro-3-picoline, Purification by fractional distillation is required. These two patents covered 2-chloro-5-substituted pyridine compounds including 2...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D213/61B01J31/22
CPCB01J31/249B01J2531/827C07D213/61
Inventor 赵立人何明赵怡敏陈雪梅林云吴秋娟
Owner SUZHOU SHIYA BIOPHARMLS
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