Reference of 1546-79-8, These common heterocyclic compound, 1546-79-8, name is 2,2,2-Trifluoro-1-(1H-imidazol-1-yl)ethanone, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.
Ethylmagnesium bromide (3M in ethyl ether, 3.95 ml, 11.84 mmol) is added dropwise to example 21a (1.6 g, 5.92 mmol) dissolved in anhydrous THF (20 mL) cooled to 0 C. Stirring is continued at 0 C. for 15 min then overnight at room temperature. The reaction mixture is cooled to 0 C. and methylmagnesium bromide (3M in ethyl ether, 1.97 ml, 5.92 mmol) is added dropwise. Stirring is continued at 0 C. for 15 min followed by 2 h at room temperature. The reaction mixture is cooled to 0 C., aqueous NH4Cl is added dropwise and stirring is continued for 5 min EtOAc is added, the organic layer separated, washed with brine, dried over Na2SO4 and concentrated under reduced pressure to furnish 1.37 g of crude ketone. Lithium bis(trimethylsilyl)amide (1.8M, 1.03 mL, 1.86 mmol) is added dropwise to the crude ketone (370 mg, 1.55 mmol) dissolved in anhydrous THF (10 mL) and cooled to -78 C. Stirring is continued at -20 C. for 1 h. The reaction mixture is cooled to -78 C. and 1-(trifluoroacetyl)imidazole (0.70 ml, 6.18 mmol) is added. Stirring is continued 3 h at room temperature. Aqueous NH4Cl solution and EtOAc are added, the organic layer is separated, dried over a phase-separator cartridge and concentrated under reduced pressure to furnish a residue that is purified by Si flash chromatography (5-40% EtOAc/Hexane as eluent) to obatain 190 mg of intermediate. Hydroxylamine hydrochloride (512 mg, 7.37 mmol) is added to such product dissolved in MeOH (20 mL) and the reaction mixture refluxed for 2 h. Volatiles are evaporated under reduced pressure, the residue is partitioned between EtOAc and saturated NaHCO3, the organic layer is separated, washed with saturated NaHCO3, dried over phase separator cartridge and concentrated under reduced pressure to furnish a 90 mg of residue. TEA (50 muL, 0.36 mmol) followed by methanesulfonyl chloride (26 muL, 0.33 mmol) are added to such residue dissolved in DCM (10 mL) and cooled to 0 C. Stirring is continued at room temperature then further TEA (50 muL, 0.36 mmol) and methanesulfonyl chloride (26 muL, 0.33 mmol) are added and stiffing is continued for 2 h. Water and DCM are added, the aqueous layer is further extracted with DCM, the organic layers are combined, dried over a phase-separator cartridge and concentrated under reduced pressure. The resulting residue is purified by flash chromatography (eluent 0-10% EtOAc/hexane) to furnish the title compound (20 mg, 23% on the last step).
The synthetic route of 1546-79-8 has been constantly updated, and we look forward to future research findings.
Reference:
Patent; BOEHRINGER INGELHEIM INTERNATIONAL GMBH; GIOVANNINI, Riccardo; BERTANI, Barbara; FERRARA, Marco; LINGARD, Iain; MAZZAFERRO, Rocco; ROSENBROCK, Holger; US2013/197011; (2013); A1;,
Imidazole – Wikipedia,
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