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Stage #1: at 30℃; for 5 h; Stage #2: at 10℃; for 2 h; Stage #3: at 30℃; for 2 h;
In three 500 ml flask, 130 g of ethyl acetoacetate (1 mole), Styrene-DVB (D301T) 39 g resin, reaction at 30 5 hours, 100 ml of distilled water, stirring the ammonia released 85 g (5 mol), reacted at 10 deg.] C after 2 hours with stirring chlorine gas at 142 g (2 mol), reacted at 30 2 hours and filtered Styrene-DVB (D301 T) and the resin solid cake was washed with NaOH (10percent concentration) was washed with an aqueous solution of 100 ml, Styrene-DVB (D301T) resin is recyclable. The filtrate was distilled to remove a small amount of ethanol, allowed to stand to crystallize, filtered and dried to give the desired product 87.8 g, 91.5percent yield.
Reference：
[1] Patent: CN105753776, 2016, A, . Location in patent: Paragraph 0009; 0020; 0021
Particularly preferred compounds of formula (II) include 3,5-dichloro-2,6-dimethyl-4-pyridinol; 3,5-dibromo-2,6-dimethyl-4-pyridinol; 3,5-dichloro-2,6-dipropyl-4-pyridinol and 3,5-dibromo-2,6-dipropyl-4-pyridinol.
Representative examples include, but are not limited to: ... arsanilic acid buquinolate carbadox carbarsone clopidol coumaphos decoquinate dichlorvos ...
Particularly preferred compounds of formula (II) include 3,5-dichloro-2,6-dimethyl-4-pyridinol; 3,5-dibromo-2,6-dimethyl-4-pyridinol; 3,5-dichloro-2,6-dipropyl-4-pyridinol and 3,5-dibromo-2,6-dipropyl-4-pyridinol.
3
[ 141-97-9 ]
[ 2971-90-6 ]
Yield
Reaction Conditions
Operation in experiment
91.5%
In three 500 ml flask, 130 g of ethyl acetoacetate (1 mole), Styrene-DVB (D301T) 39 g resin, reaction at 30 5 hours, 100 ml of distilled water, stirring the ammonia released 85 g (5 mol), reacted at 10 deg.] C after 2 hours with stirring chlorine gas at 142 g (2 mol), reacted at 30 2 hours and filtered Styrene-DVB (D301 T) and the resin solid cake was washed with NaOH (10% concentration) was washed with an aqueous solution of 100 ml, Styrene-DVB (D301T) resin is recyclable. The filtrate was distilled to remove a small amount of ethanol, allowed to stand to crystallize, filtered and dried to give the desired product 87.8 g, 91.5% yield.
With N-chloro-succinimide; In methanol; dichloromethane; at 20℃;Inert atmosphere;
A suspension of 2, 6-dimethylpyridin-4-ol (CAS: 13603-44-6; 1.00 g, 8.12 mmol) andN- chlorosuccinimide (1.46 g, 10.9 mmol) in a mixture of MeOH (10 ml) and DCM (25 ml) was stirred under inert atmosphere at room temperature overnight. The precipitate was filtered and the filtrate was concentrated to dryness. The residue was triturated with CH3CN. The precipitate was filtered, washed with CH3CN, and dried under vacuum to yield a mixture of intermediates 76 and 77 (940 mg ,73%) as a white solid. PREPARATION OF INTERMEDIATE 78 DBAD (CAS: 870-50-8; 1.52 g, 6.60 mmol) was added to a mixture of intermediates 76 and 77 (800 mg, 5.08 mmol), l-Boc-4-hydroxypiperidine (CAS: 109384-19-2; 1.33 g, 6.60 mmol) and triphenylphosphine (1.73 g, 6.60 mmol) in toluene (16 mL). The reaction mixture was stirred at room temperature for 1 h and at 85 C for 1 h. The reaction mixture was concentrated to dryness and the residue was purified by flash column chromatography (silica, heptane/EtOAc, gradient from 100:0 to 70:30). The desired fractions were collected and concentrated in vacuo to afford intermediate 78 (3.7 g, 77%, 36% purity).
α-Fluoro-β-ketone Ethers 5a-x; General Procedure
General procedure: A reaction tube containing a magnetic stir bar was charged with α-bromo-α-fluoroketone 1 (0.2 mmol, 1.0 equiv), phenol 4 (0.22 mmol,1.1 equiv) and K3PO4 (0.4 mmol, 2.0 equiv). After CH3CN (2.0 mL) had been added, the reaction tube was capped with a rubber stopper and the contents were stirred for 1-2 h at room temperature. The reaction mixture was then quenched with saturated aqueous NH4Cl solution and extracted with ethyl acetate. The combined organic phases were dried over Na2SO4, filtered and concentrated under vacuum. The crude product was purified by flash column chromatography on silica gel (PE/EtOAc = 10:1 to 100:1) to give the α-fluoro-β-ketone ether 5a-x.
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