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Chemical Structure| 1160018-61-0 Chemical Structure| 1160018-61-0

Structure of 1160018-61-0

Chemical Structure| 1160018-61-0

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Product Details of [ 1160018-61-0 ]

CAS No. :1160018-61-0
Formula : C8H10ClNO
M.W : 171.62
SMILES Code : CCCOC1=NC=C(Cl)C=C1
MDL No. :MFCD19689764

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Application In Synthesis of [ 1160018-61-0 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 1160018-61-0 ]

[ 1160018-61-0 ] Synthesis Path-Downstream   1~1

  • 1
  • [ 71-23-8 ]
  • [ 1480-65-5 ]
  • [ 1160018-61-0 ]
YieldReaction ConditionsOperation in experiment
98% A 12 L three-neck round-bottom flask with a mechanical stirrer, thermocouple, addition funnel, nitrogen inlet, and a drying tube were equipped and placed into a cooling bath. An oversized flask was used due to the large amount of foaming and effervescence during the additions. The flask was charged with tetrahydrofuran (THF, 1.8 L), and stirring was initiated. Sodium hydride was added in portions. A mild exotherm was observed initially due to residual moisture in the solvent. After this had subsided the bulk of the material was added. The reaction mixture was cooled to 0-5° C. using an ice/water bath, and a solution of propanol (103 mL) in THF (350 mL) was added slowly over a 1 hour period at a rate to keep the internal temperature below 5° C. The addition was strongly exothermic and accompanied by the evolution of hydrogen gas. There was a significant delay (45 mins) to the hydrogen release, which was sudden and caused foaming. After the complete addition of propanol, the reaction was stirred for a further 1 h. A solution of <strong>[1480-65-5]5-chloro-2-fluoropyridine</strong> (22, 86 g) in tetrahydrofuran (THF, 350 mL) was added slowly over a 1.5 hour period at a rate to keep the internal temperature below 5° C. The addition was strongly exothermic and accompanied by the evolution of hydrogen gas. There was a significant delay (45 mins) to the hydrogen release, which was sudden and caused foaming. The cooling bath was allowed to expire naturally overnight. Stirring was continued at ambient temperature until the reaction was complete, i.e., typically after overnight stirring without the requirement for additional reagents and when no starting material was observed. If reaction was not complete, it was cooled back to 0-5° C. and treated with fresh sodium hydride (0.5 eq.), the reaction was stirred at ambient temperature overnight, resampled, and the reaction was continued until deemed to be complete. The reaction was monitored by TLC (SiO2, 25percent ethyl acetate in heptanes, UV) by diluting an aliquot of reaction mixture (1 mL) with water (2 mL), extracting with ethyl acetate, and spotting the organic layer. The starting material had retention factor (RF)=0.38; the product had RF=0.45. Materials used in the synthesis are detailed in Table 3. To isolate 5-chloro-2-propoxypyridine (23), the reaction mixture was cooled to 0-5° C. using an ice/water bath. The reaction was quenched by the addition of a slow stream of saturated aqueous ammonium chloride solution (1 L). The addition was exothermic and may be accompanied by hydrogen gas evolution. The mixture was extracted with ethyl acetate (2.x.2 mL). The combined organic extracts were washed with saturated brine solution (1 L), dried over magnesium sulfate and charcoal, and filtered through a glass fiber filter. The filtrate was concentrated under reduced pressure to give a pale yellow liquid.The reaction was successfully carried out on multi-gram scale giving both excellent yield and purity, and the results are shown in Table 4. 5-Chloro-2-propoxypyridine (23) (lot No. 1357-96-1) was a pale yellow liquid, synthesized with a yield of 110 g/98percent. 5-Chloro-2-propoxypyridine (23) was analyzed using HPLC, and according to results, it was 99.0percent pure. 1H-NMR (300 MHz, CDCl3) was also used to analyze 5-chloro-2-propoxypyridine (23), confirming the identity of the compound.
 

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