Electric Literature of 1546-79-8,Some common heterocyclic compound, 1546-79-8, name is 2,2,2-Trifluoro-1-(1H-imidazol-1-yl)ethanone, molecular formula is C5H3F3N2O, 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.
Example 22b (racemic mixture)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 0C. Stirring is continued at 0C for 15 min then overnight at room temperature. The reaction mixture is cooled to 0C and methylmagnesium bromide (3M in ethyl ether, 1.97 ml, 5.92 mmol) is added dropwise. Stirring is continued at 0C for 15 min followed by 2h at room temperature. The reaction mixture is cooled to 0C, aqueous NH4C1 is added dropwise and stirring is continued for 5 min. EtOAc is added, the organic layer separated, washed with brine, dried over Na2SC”4 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 -78C. Stirring is continued at -20C for lh. The reaction mixture is cooled to -78C and l-(trifluoroacetyl)imidazole (0.70 ml, 6.18 mmol) is added. Stirring is continued 3 h at room temperature. Aqueous NH4C1 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. Hydro xylamine hydrochloride (512 mg, 7.37 mmol) is added to such product dissolved in MeOH (20 mL) and the reaction mixture refluxed for 2h. Volatiles are evaporated under reduced pressure, the residue is partitioned between EtOAc and saturated NaHCC>3, the organic layer is separated, washed with saturated NaHCC>3, dried over phase separator cartridge and concentrated under reduced pressure to furnish a 90mg of residue. TEA (50 mu, 0.36 mmol) followed by methanesulfonyl chloride (26 mu, 0.33 mmol) are added to such residue dissolved in DCM (10 mL) and cooled to 0C. Stirring is continued at room temperature then further TEA (50 mu, 0.36 mmol) and methanesulfonyl chloride (26 mu,, 0.33 mmol) are added and stirring is continued for 2h. 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).
These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 2,2,2-Trifluoro-1-(1H-imidazol-1-yl)ethanone, its application will become more common.
Reference:
Patent; BOEHRINGER INGELHEIM INTERNATIONAL GMBH; GIOVANNINI, Riccardo; BERTANI, Barbara; FERRARA, Marco; LINGARD, Iain; MAZZAFERRO, Rocco; ROSENBROCK, Holger; WO2013/17657; (2013); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem