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Chemical Structure| 479612-36-7 Chemical Structure| 479612-36-7

Structure of 479612-36-7

Chemical Structure| 479612-36-7

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Product Details of [ 479612-36-7 ]

CAS No. :479612-36-7
Formula : C7H8ClNO
M.W : 157.60
SMILES Code : OCC1=CC(Cl)=NC=C1C
MDL No. :MFCD15143398

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Application In Synthesis of [ 479612-36-7 ]

* 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 [ 479612-36-7 ]

[ 479612-36-7 ] Synthesis Path-Downstream   1~1

  • 1
  • [ 1308298-23-8 ]
  • [ 479612-36-7 ]
  • [5-methyl-2-[2-(trifluoromethyl)pyrimidin-5-yl]pyridin-4-yl]methanol [ No CAS ]
YieldReaction ConditionsOperation in experiment
78% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In 1,4-dioxane; water; at 25 - 80℃; for 2.0h;Large scale; Compound 1(a) (5-methyl-2-(2-(trifluoromethyl)pyrimidin-5-yl)pyridin-4- yl)methanol was prepared from compound l0C(i) (2-chloro-5-methylpyridin-4-yl)methanol and compound 8 2-(trifluoromethy l)pyrimi din-5 -ylboronic acid as follows:,4-dioxane (52.73 kg, 7.22 kg/kg compound l0C(i)) and water (36.5 kg, 5 kg/kg compound l0C(i)) was charged into a first inerted, stirred reactor and stirred. Potassium carbonate (11.9 kg, 1.63 kg/kg compound l0C(i)) was charged into the first reactor followed by compound lOC(i) (7.3 kg, 93 moles). The temperature of the mixture was adjusted to 25-30 C and the first reactor was further charged with [l,l?-Bis(diphenylphosphino) ferrocene] palladium (II) chloride (0.505 kg, 0.07 kg/kg compound l0C(i)). Nitrogen was bubbled through the solution for 1-2 hours before the solution was heated to 75-80 C and stirred for 2 hours.The first reactor contents were sampled and tested for compound l0C(i) content by HPLC Method-011. Sampling and LC testing was continued (with 30 minute intervals) until the compound l0C(i) content was less than 5.0%.The reaction mixture was cooled to 45 C and the first reactor contents was distilled under reduced pressure in order to reach a volume of 3 L/kg while maintaining the temperature of the reactor below 60 C. Water was charged (58.4 kg, 8.0 kg/kg compound 2C) into the first reactor followed by methyl tert-butyl ether (54 kg, 7.4 kg/kg compound l0C(i)) and the mixture was stirred for at least 10 minutes. Agitation was stopped and the mixture was allowed to settle for at least 10 minutes. The bottom aqueous layer was removed and transferred to a first vessel and the organic layer was drained to a second vessel. The aqueous phase was charged to the first reactor followed by methyl /-butyl ether (27 kg, 3.7 kg/kg compound l0C(i)) and the mixture was stirred for at least 10 minutes. Agitation was stopped and mixture was allowed to settle for at least 10 minutes. The bottom aqueous layer was removed and transferred to the first vessel and the organic layer was drained to the second vessel. The aqueous phase was charged to the first reactor followed by methyl /-butyl ether (27 kg, 3.7 kg/kg compound l0C(i)) and the mixture was stirred for at least 10 minutes. Agitation was stopped and mixture was allowed to settle for at least 10 minutes. The bottom aqueous layer was removed and transferred to the first vessel.The organic phase in the second vessel was charged into the first reactor followed by silica gel (3.65 kg, 0.50 kg/kg compound l0C(i)), and the reactor contents was stirred for at least 2 hours at 25-30 C. The reactor contents were filtered, and the filtrate was collected in a third vessel. The first reactor was rinsed with methyl /-butyl ether (27 kg, 3.7 kg/kg compound l0C(i)) which was then filtered through the filter cake and collected in the third vessel. The filtrate in the third vessel was charged into a second reactor.The contents of the second reactor were distilled under reduced pressure in order to reach a volume of 2 L/kg while maintaining the temperature of the reactor below 50 C. Heptane (25 kg, 3.42 kg/kg compound l0C(i)) was charged into the second reactor and the contents of the second reactor were distilled under reduced pressure in order to reach a volume of 4 L/kg while maintaining the temperature of the reactor below 50 C. Charging the second reactor with heptane and distilling the reactor contents as described was repeated two more times. The second reactor was then charged with dichloromethane (14.56 kg, 2.0 kg/kg compound l0C(i)) and the mixture was stirred for at least 2 hours at 25-30 C. The contents of the second reactor were filtered and the filter cake and reactor was washed with a mixture of dichloromethane (3.24 kg, 0.44 kg/kg compound l0C(i)) and heptane (3.32 kg, 0.45 kg/kg compound l0C(i)). The filter cake was dried under vacuum at 30-40 C for 14 hours to give crude compound 1(a) (-10 kg). Dichloromethane was charged (26.6 kg, 3.64 kg/kg compound l0C(i)) into an inerted third reactor, followed by the crude compound 1(a) (-10 kg). The reactor contents were heated to 35-45 C and stirred for at least 2 hours. Heptane was charged (27.36, 3.75 kg/kg compound l0C(i)) into the third reactor over a period of 3 hours. The mixture was cooled to 20-30 C and this temperature was held for at least 2 hours. The solids were filtered and filter cake was washed with a mixture of dichloromethane (4.44 kg, 0.61 kg/kg compound l0C(i)) and heptane (4.55 kg, 0.62 kg/kg compound l0C(i)). The solids were dried in a vacuum oven at 30-40 C for at least 14 hours to give compound 1(a) (8.53 kg, 78% yield). The purity of the product was determined to be 98.71 A% using analytical HPLC Method-Ol l.
 

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