Electric Literature of 112758-40-4, As we all know, there are many different methods for the synthesis of a compound, and people can choose the synthesis method that suits their own laboratory according to the actual situation. 112758-40-4 name is 3-Methyl-1H-pyrazole-4-carbaldehyde, This compound is widely used in many fields, so it is necessary to find a new synthetic route. The downstream synthesis method of this compound is introduced below.
A mixture of 3 -methyl- lH-pyrazole-4-carbaldehyde (5 g, 45.41 mmol), potassium carbonate (9.41 g, 68.11 mmol), 2,3-difluorobenzonitrile (6.06 mL, 54.5 mmol) and dimethylformamide (50 mL) is stirred at 100C for 5 hr. and then at room temperature overnight. Water is added and a precipitated is formed. The precipitate is filtered. The aqueous solution filtered is extracted in ethyl acetate. Organic layer is washed with brine, dried over magnesium sulfate and solvent is evaporated. Both the solid precipitated and the solid recovered from organic layer after evaporation are combined and 10.4 g of the title compound is obtained and used with no further purification (the title compound is contaminated with the other pyrazole regioisomer in a ratio 90: 10). MS (m/z): 230 (M+l). To a suspension of 2-chloro-4,4-difluoro-spiro[5H-thieno[2,3-c]pyran-7,4′- piperidine] hydrochloride (1.3 g, 4.11 mmol) in 1,2-dichloroethane (20.5 mL) is added triethylamine (0.75 mL, 5.3 mmol) and 3-fluoro-2-(4-formyl-3-methyl-pyrazol-l-yl)- benzonitrile (as major compound in a mixture of regioisomers) (1.13 g, 4.93 mmol). The mixture is stirred at room temperature for 30 min. Then, sodium triacetoxyborohydride (1.82 g, 8.22 mmol) is added. The mixture is stirred at room temperature overnight. After that time, solvent is evaporated and the residue is diluted with methanol and purified using a 50 g SCX cartridge and then by normal phase Isco chromatography eluting with dichloromethane and methanol to give 1.6 g of a crude material containing a mixture of regioisomers (80:20 aprox). This residue is further purified by reverse phase HPLC to give 927 mg of 2-[4-[(2-chloro-4,4-difluoro-spiro[5H-thieno[2,3-c]pyran-7,4′-piperidine]- r-yl)methyl]-3-methyl-pyrazol-l-yl]-3-fluoro-benzonitrile as the major regioisomer. MS (m/z): 493 (M+l).
At the same time, in my other blogs, there are other synthetic methods of this type of compound, 3-Methyl-1H-pyrazole-4-carbaldehyde, and friends who are interested can also refer to it.