1-(2,5-DICHLORO-PHENYL)-2,2,2-TRIFLUORO-ETHANONE

l-(2, 5-Dichloro-phenyl)-2, 2, 2-trifluoro-ethanone A solution of 1 , 4-dichlorobenzene (20 g, 136 mmol) in anhydrous THF (200 mL) was cooled to -78 °C. n-BuLi (150 mmol in 60 mL hexane) was added. The mixture was stirred for 1 h, followed by addition of methyl trifluoroacetate (18 mL, 179 mmol) in 30 min. The mixture was allowed to warm up to 0 °C and then stirred for 2 h. Pre-cooled saturated aqueous ammonium chloride solution (100 mL) was added. The phases were separated. The organic phase was concentrated under vacuum and the residue was dissolved in ethyl acetate (200 mL). The water phase was extracted with ethyl acetate (200 mL). The two ethyl acetate phases were combined and then washed with brine (200 mL). The phases were separated. The organic phase was dried over Nal-(2, 5-Dichloro-phenyl)-2, 2, 2-trifluoro-ethanoneA solution of 1 , 4-dichlorobenzene (20 g, 136 mmol) in anhydrous THF (200 mL) was cooled to -78 °C. n-BuLi (150 mmol in 60 mL hexane) was added. The mixture was stirred for 1 h, followed by addition of methyl trifluoroacetate (18 mL, 179 mmol) in 30 min. The mixture was allowed to warm up to 0 °C and then stirred for 2 h.Pre-cooled saturated aqueous ammonium chloride solution (100 mL) was added. The phases were separated. The organic phase was concentrated under vacuum and the residue was dissolved in ethyl acetate (200 mL). The water phase was extracted with ethyl acetate (200 mL). The two ethyl acetate phases were combined and then washed with brine (200 mL). The phases were separated. The organic phase was dried over Nal-(2, 5-Dichloro-phenyl)-2, 2, 2-trifluoro-ethanoneA solution of 1 , 4-dichlorobenzene (20 g, 136 mmol) in anhydrous THF (200 mL) was cooled to -78 °C. n-BuLi (150 mmol in 60 mL hexane) was added. The mixture was stirred for 1 h, followed by addition of methyl trifluoroacetate (18 mL, 179 mmol) in 30 min. The mixture was allowed to warm up to 0 °C and then stirred for 2 h.Pre-cooled saturated aqueous ammonium chloride solution (100 mL) was added. The phases were separated. The organic phase was concentrated under vacuum and the residue was dissolved in ethyl acetate (200 mL). The water phase was extracted with ethyl acetate (200 mL). The two ethyl acetate phases were combined and then washed with brine (200 mL). The phases were separated. The organic phase was dried over NaGeneral procedure: To a chilled to –75 °C solution of 1, 4-dichlorobenzene (10.0 g, 68 mmol) in anhydrous THF (150 mL), BuGeneral procedure: To a stirred suspension of sodium azide (2.08 g, 32 mmol) in DMF (60 mL), 2, 2, 2-trifluoro-1-(2-fluorophenyl)ethanone 2aF (5.76 g, 30 mmol) was added. Heating the suspension to 90 C resulted information of nearly clear solution. During further heating, the formation of a heavy precipitate (NaF) was observed. The reaction course was monitored by 19F NMR spectroscopy. After complete consumption of the starting 2, 2, 2-trifluoro-1(2-fluorophenyl)ethanone 2aF (complete disappearance of its signals inthe NMR spectrum of the reaction mixture was observed after 4 h), the reaction mixture was cooled to 25 C and poured in coldwater (300 mL). The obtained yellow solution was extractedwith diethyl ether - petroleum ether mixture (1 : 1, 2×100 mL). The combined organics were washed with 2% aqueous citricacid (2×50 mL), brine (50 mL), dried with Na2SO4, and the drying agent was filtered off. The solvents were distilled off undernormal pressure using the Vigreux distillation column. Vacuum distillation of the residue afforded 3.6 g (64%) of compound 1a as light yellow liquid.General procedure: To a chilled to -75 C solution of 1, 4-dichlorobenzene (10.0 g, 68 mmol) in anhydrous THF (150 mL), BunLi (30 mL, 75 mmol, 2.5 M solution in hexane) was added dropwise maintaining the reaction temperature below -70 C. The reaction mixture wasstirred at -75 C for 1 h, cooled to -80 C with liquid nitrogenand then a solution of ethyl trifluoroacetate (10.8 g, 76 mmol) in THF (15 mL) was slowly added maintaining the reaction temperature below -75 C. After 30 min stirring at -75 C, thereaction mixture was warmed up to -50 C, and 10% HCl (20 mL) was added following by warming up to 0 C and additionof another portion of 10% HCl (10 mL) until distinct acidity ofthe aqueous layer was achieved. The organic layer was separated and the aqueous layer was extracted with diethyl ether (2×40 mL). The combined organics were washed with brine (2×50 mL), dried with Na2SO, and the drying agent was filtered off. The solvents were distilled off under normal pressure using the Vigreux distillation column. Vacuum distillation of the residue afforded 12.8 g (77.3%) of compound 2b as light yellow liquid. B.p. 92-100 C (10 Torr), nD20 1.4921.Example 2b:(S)-4-Cyclopr o yl-2-(2, 5-dichlor o-phenyl)- 1, 1, 1 -tr ifluor o-but-3-yn-2-olNaphthalene- 1 -sulfonic acid ((R)-2 -hydroxy- 1 -methyl-2, 2-diphenyl-ethyl)-amide (130 mg, 0.31 mmol) was charged followed by addition of anhydrous toluene (5 mL) and dimethylzinc (3.1 mmol in 3.1 mL heptane) at RT under inert atmosphere. The reaction mixture was stirred at RT for 0.5 h followed by addition ofethynylcyclopropane (260 mg, 2.8 mmol). The reaction mixture was stirred at RT for 1.5 h. A solution of l-(2, 5-dichloro-phenyl)-2, 2, 2-trifluoro-ethanone (500 mg, 2.1 mmol), prepared according to example 1, in anhydrous toluene (5 mL) was charged at RT over a period of 2 h. The reaction mixture was then stirred at RT for 18 h followed by addition of saturated aqueous ammonium chloride solution (20 mL). The phases were separated. The water phase was extracted with ethyl acetate (2 times with 20 mL). The combined organic phase was washed with brine (20 mL) and dried over Na2S04. The mixture was filtered and concentrated under vacuum. The residue was purified via column chromatography using silica gel eluting with dichloromethane / hexane (1/10 v/v) to afford after isolation and drying(S)-4-cyclopropyl-2-(2, 5-dichloro-phenyl)- 1, 1, 1 -trifluoro-but-3-yn-2-ol (500 mg, 78% yield) as a light yellow oil. The ee measured was 46 % (HPLC method description A).1H NMR (400 MHz, CDC13) delta 7.90 (d, J = 2.4 Hz, 1 H), 7.38 (d, J = 8.8 Hz, 1 H), 7.30 (dd, J = 8.8, 2.4 Hz, 1 H), 3.52 (s (br), 1 H), 1.39 to 1.36 (m, 1 H), 0.89 to 0.83 (m, 4 H).

Molecular Weight:243.01
XLogP3:4
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:1
Exact Mass:241.9513046
Monoisotopic Mass:241.9513046
Topological Polar Surface Area:17.1
Heavy Atom Count:14
Complexity:229
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes