Method for preparing 3-halo-1-(3-chloro -2-pyridyl)-1H-pyrazole-5-formyl halide
A pyridyl, formyl halide technology, applied in the field of preparing 3-halogenated-1--1H-pyrazole-5-formyl halide, can solve the problems of dangerous oxidation operation, long steps, large amount of waste water and the like
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Embodiment 1
[0036] Example 1: Synthesis of 3-chloro-1-(3-chloro-2-pyridyl)-1H-pyrazole-5-formyl chloride
[0037] Step 1: Synthesis of 3-chloro-1-(3-chloro-2-pyridyl)-4,5-dihydro-1H-pyrazole-5-carboxylic acid
[0038]
[0039] Add 3-chloro-1-(3-chloro-2-pyridyl)-4,5-dihydro-1H-pyrazole-5-carboxylic acid ethyl ester (70.0 g, 210.4 mmol ), THF (250 milliliters), water (250 milliliters), sodium hydroxide (12.6 grams, 315.0 millimoles), react at room temperature for 6 hours, remove THF under reduced pressure, add water (250 milliliters) and ethyl acetate (80 milliliters) Extraction, the inorganic phase was acidified with hydrochloric acid to pH = 2, and then extracted with dichloromethane (200 ml × 3 times), the organic phase was extracted with anhydrous MgSO 4 Drying, desolvation under reduced pressure gave 44.1 grams of white crystalline powder, HPLC normalized content of 98% (analysis conditions: chromatographic column is ZORBAX Eclipse XDB-C8 4.6 * 150mm 5 μm, mobile phase is acetonit...
Embodiment 2
[0045] Example 2: Synthesis of 3-chloro-1-(3-chloro-2-pyridyl)-1H-pyrazole-5-formyl chloride
[0046]
[0047] Add 3-chloro-1-(3-chloro-2-pyridyl)-4,5-dihydro-1H-pyrazole-5-carboxylic acid (the product of step 1 of Example 1, 26.6 g, 100.0 mmol), n-hexane (500 ml), phosphorus pentachloride (210.0 g, 1000.0 mmol), reflux reaction for 8 hours, cooled to room temperature, filtered, and the filtrate was precipitated under reduced pressure to obtain 25.0 g of brown oil , the HPLC normalized content was 95%, and the yield was 85%.
[0048] 1 H NMR (300MHz, CDCl 3 ) δ (ppm) 8.510 (dd, 1H), 7.945 (dd, 1H), 7.488 (dd, 1H), 7.213 (s, 1H).
Embodiment 3
[0049] Example 3: Synthesis of 3-chloro-1-(3-chloro-2-pyridyl)-1H-pyrazole-5-formyl chloride
[0050]
[0051] Add 3-chloro-1-(3-chloro-2-pyridyl)-4,5-dihydro-1H-pyrazole-5-carboxylic acid (the product of step 1 of Example 1, 6.2 grams, 23.4 millimoles), thionyl chloride (40.0 grams, 332.8 millimoles), reflux reaction for 6 hours, precipitation under reduced pressure, obtained 5.7 grams of brown oil, HPLC normalized content was 98%, yield was 86% .
[0052] 1 H NMR (300MHz, CDCl 3 ) δ (ppm) 8.510 (dd, 1H), 7.947 (d, 1H), 7.490 (dd, 1H), 7.211 (s, 1H).
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