[F:1][C:2]([F:12])([F:11])[C:3](=O)[CH2:4][C:5]([O:7][CH2:8][CH3:9])=[O:6].[CH2:13]=O.[CH3:15][NH:16][NH2:17].Cl>C(O)C>[CH2:8]([O:7][C:5]([CH:4]1[CH2:15][N:16]([CH3:13])[N:17]=[C:3]1[C:2]([F:12])([F:11])[F:1])=[O:6])[CH3:9]Ethyl 4,4,4-trifluoroacetoacetate (120 g, 0.65 mol) was dissolved in 650 ml of ethanol and the solution was cooled down to 0° C. A 37% aqueous solution of formaldehyde (53 g, 0.65 mol) was added and the mixture was stirred for 15 minutes at 0° C. Methylhydrazine (30 g, 0.65 mol) was added and the reaction mixture was heated to reflux. After reaching the reflux temperature, 2.5 ml of concentrated hydrochloric acid were added, and refluxing was continued for 16 h. Subsequently, the mixture was cooled down and the solvent was removed in vacuo. The remainder was taken up in water and extracted with ethyl acetate. The combined organic layer was washed with water, dried over magnesium sulfate and evaporated. The remaining oil was purified by silica gel chromatography using ethyl acetate and hexane as eluents, yielding 90 g of 1-methyl-3-trifluoromethyl-4,5-dihydro-1H-pyrazole-4-carboxylic acid ethyl ester.
Wird geladen…
