Synthetic Route of 112758-40-4, In the next few decades, the world population will flourish. As the population grows rapidly and people all over the world use more and more resources, all industries must consider their environmental impact. 112758-40-4, name is 3-Methyl-1H-pyrazole-4-carbaldehyde belongs to pyrazoles-derivatives compound, it is a common compound, a new synthetic route is introduced below.
To a solution of 3 -methyl- lH-pyrazole-4-carbaldehyde (1 g, 9.08 mmol) in acetonitrile (10 mL) is added potassium carbonate (1.76 g, 12.71 mmol) and 2,3- difluornitrobenzene (1.73 g, 10.90 mmol) and the mixture is stirred at room temperature overnight. Water is added and the organic phase is extracted with ethyl acetate. Organic layer is dried over sodium sulfate and the solvent evaporated under reduced pressure. The residue is purified by normal phase Isco chromatography using as eluent ethyl acetate/hexane (20-80%) to give a 62% yield of a mixture of regioisomers containing the title compound as major product that is used with no further purification. NMR is consistent with desired structure, although mixture of regiosomers is detected: NMR (MeOD): 9.98 (s, 1H), 8.65 (d, 1H, J= 1.6 Hz), 7.99-7.26 (m, 3H), 2.49 (s, 3H). A solution of 2-chloro-4,4-difluoro-spiro[5H-thieno[2,3-c]pyran-7,4′-piperidine] (2.1 g, 7.5 mmol) and l-(2-fluoro-6-nitro-phenyl)-3-methyl-pyrazole-4-carbaldehyde (3 g) (as major compound in a mixture of regioisomers in the pyrazole) in dichloromethane (47 mL) is stirred at room temperature for 30 minutes. Then, sodium triacetoxy borohydride (3.94g) is added and the mixture is stirred overnight at that temperature. The reaction mixture is quenched carefully with sodium bicarbonate (saturated solution) and extracted with dichloromethane. Organic layer is washed with brine, decanted and dried over sodium sulfate. Solvent is evaporated and the residue is purified by normal phase Isco chromatography using as eluant dichloromethane and isopropanol to give 2.28 g of 2-chloro-4,4-difluoro- -[[l-(2-fluoro-6-nitro-phenyl)-3-methyl-pyrazol-4- yl]methyl]spiro[5H-thieno[2,3-c]pyran-7,4′-piperidine] (the compound is contaminated with the other pyrazole regioisomer in a ratio 80:20). MS (m/z): 513 (M+l). To a solution of 2-chloro-4,4-difluoro-l’-[[l-(2-fluoro-6-nitro-phenyl)-3-methyl- pyrazol-4-yl]methyl]spiro[5H-thieno[2,3-c]pyran-7,4′-piperidine] (2.28g, 4.46 mmol) and iron (2.5g) in ethanol (1 lmL) and water (1 lmL), a few drops of acetic acid is added. The reaction mixture is stirred at 90C for 70 min. The mixture is then filtered over celite and concentrated under vacuum. Remained solution is basified with sodium bicarbonate(saturated solution) and extracted with dichloromethane. Organic layer is decanted, dried over sodium sulfate and solvent evaporated to obtain 1.8 g of 2-[4-[(2-chloro-4,4- difluoro-spiro[5H-thieno[2,3-c]pyran-7,4′-piperidine]- -yl)methyl]-3-methyl-pyrazol-l- yl]-3-fluoro-aniline that is used in next step without further purification (the compound is contaminated with the other pyrazole regioisomer in a ratio 80:20). MS (m/z): 483 (M+l).
The synthetic route of 3-Methyl-1H-pyrazole-4-carbaldehyde has been constantly updated, and we look forward to future research findings.