4,4,4-Trifluoro-1-(2-furanyl)-1,3-butanedione

clear yellow liquid

Into a 500 mL flask was weighed 20.0 g (181.6 mmol) of 2-acetylfuran, 50 mL of THF, and 24 mL of ethyl trifluoroacetate. The resulting solution was cooled to 0-3 °C in an ice bath and 1.0 M LiHMDS was added (200 mL). The reaction was allowed to warm to room temperature where it remained overnight. The reaction was then concentrated in vacuo to remove THF and the residue was washed into a separatory funnel with ethyl acetate and 1.0 M HCl. The ethyl acetate was separated, washed with brine, dried (NaGeneral procedure: Ethyl trifluoroacetate 9 (0.047 mol) and 2-acetyl furan (0.047 mol) were added dropwise to a solution of ethanol (55 mL) containing thinly sliced sodium (0.047 mol), and stirred over night at room temperature. Then, the solution was poured in ice-water containing concentrated sulfuric acid. The solution was extracted with dichloromethane, dried, concentrated and purified on a column of silica using a 10percent gradient of ethyl acetate in hexanes to afford 10 (82.6percenty). 10(0.020 mmol) was added drop wise into a solution of hydrazinobenzene(0.020 mmol), ethanol(50ml)and acetic acid(0.5 ml), then refluxed.The cooled mixture was concentrated under vacumm and the pyrazole11(66.7percenty) was obtained after purification by silicagel(a5percentgradient of ethyl acetate in hexanes). Pyrazole 11(0.043mol) was dissolved in acetone (120 ml) and KMnO4(0. 071mmol) was added. This mixture was heated at 60°C for 3 h and cooled to room temperature.Then isopropyl alcohol was added and stirred at room temperature overnight. The reaction mixture was filtered and concentrated. The residue was dissolved in 1N NaOH, washed and acidified with 2N HCl solution to obtain 12(46.3 percent y).The amide derivatives 13-14 were prepared through acyl chlorides derived from 12. A solution of 12 (0.004mol) in thionyl chloride(10mL) was refluxed for 5 hand then concentrated under vacuum. The crude acylchloride was added dropwise to a cooled solution(0°C) of substituted aniline(0.004mol) and TEA (0.008mol) in dichloromethane (10mL). The mixture was stirred over night at room temperature, and then purified on a column of silica using a gradient of e thyl acetate in hexanes to afford the pure products.[00141] Scheme 6: Synthesis of the diketone intermediate 4, 4, 4-trifluoro- 1 -(furan-2- vDbutane- 1 , 3-dione 19 6 1; [00142] The diketone 19 was synthesized from acetylfuran and trifluoracetate to obtain the 4, 4, 4-trifluoro-1-(furan-2-yl)butane-1, 3-dione 19 product as follows. 2- Acetylfuran 18 (11.0 g, 210 mmol) was dissolved in benzene (210 mL). At room temperature was added KOtBu (23.6 g, 210 mol). The resulting red solution was cooled to 5° C. Ethyl trifluoracetate 6 (25 mL, 29.8 g, 210 mmol) was added dropwise in approximately 20 minutes keeping the temperature below 15 °C. Then the mixture was stirred for 16 hours at room temperature. The mixture was poured in ice- water (300 mL) containing concentrated sulfuric acid (5 g). The aqueous mixture was extracted with tBME (3 x 200 mL). The combined organic layers were washed with brine (200 mL), dried (Na

Molecular Weight:206.12
XLogP3:1.5
Hydrogen Bond Acceptor Count:6
Rotatable Bond Count:3
Exact Mass:206.01907850
Monoisotopic Mass:206.01907850
Topological Polar Surface Area:47.3
Heavy Atom Count:14
Complexity:247
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes