2-(3,5-Bis(trifluoromethyl)phenyl)-2-methylpropion

Lithium hydroxide monohydrate (2.13 g, 50.6 mmol) was added to a suspension of methyl α, α-dimethyl-3, 5-bis(trifluoromethyl)benzeneacetate (Description 9, 5.3 g, 16.88 mmol) in methanol (60 mL), water (20 mL) and tetrahydrofuran (20 mL) and the mixture was degassed and stirred at room temperature for 3 days. The solvent was evaporated under reduced pressure and the residue was suspended in hydrochloric acid (1M). The mixture was extracted with ethyl acetate and the combined organic fractions were dried (MgSO4) and the solvent was evaporated under reduced pressure to give the title compound as a colorless solid (5.05 g, 100percent). 1H NMR (400 MHz, CDCl3) δ7.84 (2H, s), 7.80 (1H, s), and 1.68 (6H, s).Lithium hydroxide monohydrate (2.13 g, 50.6 mmol) was added to a suspension of methyl α, α-dimethyl-3, 5-bis(trifluoromethyl)benzeneacetate (Description 5, 5.3 g, 16.88 mmol) in methanol (60 mL), water (20 mL) and tetrahydrofuran (20 mL) and the mixture was degassed and stirred at room temperature for 3 days. The solvent was evaporated under reduced pressure and the residue was suspended in hydrochloric acid (1M). The mixture was extracted with ethyl acetate and the combined organic fractions were dried (MgSO4) and the solvent was evaporated under reduced pressure to give the title compound as a colorless solid (5.05 g, 100percent). 1H NMR (400 MHz, CDCl3) δ 7.84 (2H, s), 7.80 (1H, s), and 1.68 (6H, s).In S4: Methyl 2-(3, 5-bis(trifluoromethyl)phenyl)-2-methylpropanoate (20 g, 1.0 eq) was dissolved in methanol(200 g), an aqueous solution of sodium hydroxide (4 g, 2.0 eq) was added. Under nitrogen protection, the temperature of the system is raised to 100°C and refluxed.After 7h, the reaction of the raw materials was completed, and the temperature was lowered to room temperature. The organic phase was extracted by adding methyl tert-butyl ether (100 g) to the system, and the aqueous phase was concentrated.Phosphoric acid adjusted Ph = 1-2, a large number of solids precipitated, stirred for a few minutes, filtered and dried to give 2-(3, 5-bis(trifluoromethyl)benzeneBase)-2-methylpropionic acid. Yield: 90percentUnder nitrogen, the 1kg2- (3, 5- bis-trifluoromethylphenyl) acetic acid (purity 98percent, 3.5mol) was dissolved in tetrahydrofuran 15L, stirring cooled to -50 , the 4.5L n-butyl butyllithium in n-hexane (2.5mol / L, 11.25mol) carefully added dropwise to the reaction mixture, the reaction system to control temperature did not exceed -35 . After the addition of n-butyl lithium, methyl iodide was added 1.1kg (7.7 mol), After the addition, gradually raised to room temperature, the reaction continued stirring 5h. Then 10percent hydrochloric acid was added to quench the reaction, and adjusting the pH value of less than 3. Liquid separation, the aqueous layer was extracted with ethyl acetate, the combined organic layers, the organic layer was concentrated to the crude product dries. The crude product was dissolved in 2-fold weight of toluene, and stirred and heated at reflux for azeotropic removal of water until no further water was removed; system cooling crystallization, centrifugation, concentrated to 1/3 of the mother liquor after recrystallization, centrifugation, crystallization twice merge, and dried in vacuo at 50 deg.] C, to give 0.85kg2- (3, 5- bis-trifluoromethyl-phenyl) -2-methyl-propionic acid (GC purity 95.8percent), 77percent molar yieldIn a 100 mL round bottomed flask equipped with a magnetron and equipped with a reflux condenser, 5.6 g of potassium hydroxide And 25ml of ethylene glycol, stirring dissolved, adding 2.67g 2- (3, 5-bistrifluoromethylphenyl) propionitrile, reflux condenser in the end of the trachea to the exhaust gas absorption device; stirring reaction at 135 ° C for 20h , Until almost no ammonia is released, the system is cooled to room temperature; 30 ml of deionized water is added to the reaction system, and a small amount of solid insoluble matter is removed by filtration; the residue is washed with deionized water and combined with the filtrate, and the pH is adjusted to 1 with hydrochloric acid (3, 5-bistrifluoromethylphenyl) propionic acid; the crude product was recrystallized from toluene to give 2.1 g of a white solid in 73percent yield.Under room temperature, which are sequentially input to the reaction bottle crude compound 4 (530.5g, 1 . 706mol), tetrahydrofuran 5L, -5 ° C added in batches sodium hydrogen (170.6g, 4 . 265mol), with temperature stirring 1h, dropping sulfuric acid dimethyl ester (322.7g, 2 . 559mol), 50 °C reaction 10h, cooling to 10 °C dropwise 4L sodium hydroxide (204.7g, 5 . 118mol) solution, the drop finishes, 50 °C reaction 4h, cooling to room temperature, pressure reducing evaporate solvent, solid precipitating a large amount of the acidity, filtering, drying with petroleum ether acetic acid ethyl ester is recrystallized to get white solid 2 - (3, 5-bis-trifluoromethyl-phenyl) - 2-methyl-propionic acid 325.1g (three-step reaction of the total mole yield 63.5percent).

Molecular Weight:300.20
XLogP3:4.1
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:8
Rotatable Bond Count:2
Exact Mass:300.05849853
Monoisotopic Mass:300.05849853
Topological Polar Surface Area:37.3
Heavy Atom Count:20
Complexity:349
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes