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With potassium carbonate; In acetonitrile; for 3h;Reflux;
Preparation of methyl l-(2-bromoethyl)-3-(trifluoromethyl)-lH-pyrazole-5-carboxylate (33); Methyl-3-(trifluoromethyl)-lH-pyrazole-5-carboxylate (32) (1.0 g, 5.15 mmol), 1,2- dibromoethane (2.22 mL, 25.77 mmol), and K2C03 (1.42g, 10.31 mmol) were stirred in MeCN (50 mL) at reflux for 3 hours. The reaction was concentrated in vacuo. The residue was then partitioned between EtOAc and H20, and the organics were dried (Na2S04) and concentrated in vacuo to give methyl l-(2-bromoethyl)-3-(trifluoromethyl)-lH-pyrazole-5-carboxylate (33) (1.21 g, 78%); NMR (300 MHz, CDC13) delta 3.74 (t, 2H, J - 6.78 Hz), 3.94 (s, 3H), 5.02 (t, 2H, J = 6.75 Hz), 7.10 (s, 1H). The product was used without further purification
Example 9. Procedure for the synthesis of 2-(trifluoromethyl)-5-(3-((3- (trifluo (5H)-one (34); Preparation of methyl 3-(trifluoromethyl)-lH-pyrazole-5-carboxylate (32); 3-(Trifluoromethyl)-lH-pyrazole-5-carboxylic acid (31) (1.0 g, 8.33 mmol) was stirred inMeOH (50 mL) at rt. AcCl (1.18 mL, 16.67 mmol) was added dropwise, and the reaction stirred at reflux for 2 hours. The reaction was concentrated in vacuo and partitioned between EtOAc and saturated NaHC03 solution. The organics were dried (Na2S04) and concentrated in vacuo to give methyl 3-(trifluoromethyl)-lH-pyrazole-5-carboxylate (32) (1.0 g, 93%); NMR (300 MHz, CDC13) delta 3.98 (s, 3H), 7.10 (s, 1 H). The product was used without purification.
General procedure: To a 10 mL Schlenk charged with CF3CH2NH2·HCl (82 mg, 0.6 mmol) and NaNO2 (42 mg, 0.6 mmol) was added 1.0 mL of toluene and 50 muL of distilled H2O, and the resultant mixture was stirred at 0 oC for 0.5 h. Then, the alkyne 1 (0.2 mmol, 1.0 equiv.) was added to the in situ prepared CF3CHN2 solution, and the resulting mixture was stirred vigorously at room temperature for 0.5 to 1.0 h. After completion of the reaction, the mixture was quenched with distilled water (10 mL), and ethyl acetate (10 mL) was added, and filtered. The aqueous phase was extracted with ethyl acetate (2 × 10 mL). The organic layers were combined, dried anhydrous Mg2SO4 and then concentrated in vacuo. The pure product was obtained by flash column chromatography on silica gel with hexane/ethyl acetate (15/1 to 10/1, v/v) to afford the 3-trifluoromethylpyrazole 2.
2,4,4-trichloro-2-ethoxy-5,5,5-trifluoropentanoic acid methyl ester[ No CAS ]
[ 6833-82-5 ]
Yield
Reaction Conditions
Operation in experiment
72%
With water; hydrazine hydrate; In ethanol; at 20 - 26℃; for 1h;
Method A: in 26 C constant temperature in the water bath, in the three flasks, input 7.94 g (0.025 muM) 2, 4, 4 - trichloro -2 - ethoxy - 5, 5, 5 - trifluoro methyl valerate, 18.4 g ethanol (23.3 ml) and 5.4 g water (5.4 ml), stirring slowly dripping 5.5 g 85% of the hydrazine hydrate solution, dropping time is 3 minutes, and then remain at room temperature 1 hour. Recovering ethanol by distillation, the remaining product after the water washing, drying, to obtain 3.49 g 3 - (trifluoromethyl) - 1 - H - pyrazole -5 - methyl formate, the yield is 72%.
2,4-dichloro-2-ethoxy-5,5,5-trifluoropentanoic acid methyl ester[ No CAS ]
[ 6833-82-5 ]
Yield
Reaction Conditions
Operation in experiment
71.5%
With water; hydrazine hydrate; In ethanol; at 20 - 26℃; for 1h;
Method B: 26 C conditions, in three flasks, input 7.03 g (0.025 muM) 2, 4 - dichloro -2 - ethoxy - 5, 5, 5 - trifluoro -3 - alkenyl - methyl valerate, 18.4 g ethanol (23.3 ml) and 5.4 g water (5.4 ml), stirring slowly dripping 5.5 g 85% of the hydrazine hydrate solution, dropping time is 3 minutes, and then remain at room temperature 1 hour. Recovering ethanol by distillation, the remaining product after the water washing, drying, to obtain 3.47 g 3 - (trifluoromethyl) - 1 - H - pyrazole -5 - methyl formate, the yield is 71.5%.
methyl 4-bromo-3-(trifluoromethyl)-1H-pyrazole-5-carboxylate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
0.53 g
With N-Bromosuccinimide; In N,N-dimethyl-formamide; at 60℃; for 24h;
Under a nitrogen atmosphere, 0.59 g of N-bromosuccinimide was added to a mixture of 0.58 g of 3-trifluoromethyl-1H-pyrazole-5-carboxylic acid methyl ester and 10 mL of DMF, and the mixture was stirred at 60 C. for 1 day. To the obtained mixture, 1M aqueous sodium thiosulfate solution and saturated aqueous sodium hydrogen carbonate solution were added, and the mixture was extracted with tert-butyl methyl ether. The obtained organic layer was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography (hexane: ethyl acetate = 2: 1) to obtain 0.53 g of intermediate A-7 represented by the following formula. I
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