3-(4-TERT-BUTYL-PHENYL)-PROPIONICACID

Step 2: Synthesis of 3-[4-(t-butyl)phenyl] propionic acid (compound 3); 3-[4-(t-butyl)phenyl]-2-acrylic acid (530 mg, 1.3 mmol) was dissolved in anhydrous THF (12 niL), and added a catalytic amount of 10 % palladium active carbon to carry out hydrogenation, followed by stirring for 2 hours at room temperature. The resulting mixture was diluted with ether, filtered through celite pad, and then concentrated under reduced pressure to yield acidic compound (compound 3, 480 mg, 95%).1H-NMR (300MHz5 CDCl3): delta 1.29 (s, 9H), 2.69 (t, 2H, J= 7.9 Hz), 2.95 (t, 2H, J= 7.9 Hz), 7.14 (d, 2H, J= 8.2 Hz)5 7.31 (d, 2H, J= 8.4 Hz)General procedure: The appropriate acid 31 or 45 (1eq, 5.3 mmol), was dissolved in anhydrous THF (21 ml) and added of a catalytic amount of 10% palladium active carbon, followed by stirring for 4h at room temperature under H2 atmosphere. The resulting mixture was diluted with ether, filtered through a celite pad and finally concentrated under reduced pressure to give the pure title compounds.A. A sample of 3-(4-tert-butyl-phenyl)-acrylic acid (12.28 g, 60.1 mmol) was slurried in a mixture of ethanol (100 mL) and 10% palladium on carbon (0.60 g). The mixture was hydrogenated at 50 psi hydrogen for 1.5 h, then filtered over a pad of Celite. The solvents were removed in vacuo to yield 3-(4-tert-butyl-phenyl)-propionic acid as a white crystalline powder (12.28 g, 59.5 mmol). 1H NMR (d6-DMSO): delta 12.08 (s, 1H), 7.28 (d, 2H), 7.13 (d, 2H), 2.77 (t, 2H), 2.50 (t, 2H), 1.24 (s, 9H).A 125 mL Ehrlenmayer flask equipped with a magnetic stirrer bar was charged with 7.76 g (47.8 mmol) of 4-t-butylbenzaldehyde, 5.28 g (50.7 mmol) of malonic acid and 2.2 mL (2.2g, 27.2 mmol) of pyridine. The slurry was heated to 800C, at which temperature a clear yellow solution formed. After stirring for 2 hr, the reaction mixture was cooled to 25C. The resulting solid was isolated by filtration, rinsing with water (2 X 30 mL) and 2: 1 methyl t-butyl ether (MTBE)/hexanes (2 X 30 mL). A total of 3.1 g of 4-t-butylcinnamic acid was isolated.A 500 mL Parr shaker reaction vessel was charged with 3.10 g (15.2 mmol) of 4-t- butylcinnamic acid, 20 mL of ethyl acetate and 10 mL of ethanol. This mixture was treated with 0.15 g of 10% palladium on charcoal and placed under an atmosphere of 51 psig of hydrogen gas in a Parr shaker apparatus. A total of 14 psig of hydrogen was taken up in 16 hours. The reaction mixture was removed from the Parr shaker apparatus after dissipating the hydrogen gas, filtered through a Celite pad to remove the catalyst and concentrated to a white solid, 3-(4-t-butylphenyl)propanoic acid (3.07 g). IH NMR (d6- DMSO): delta 12.2, bs, IH (COOH); delta 7.16, d, 2H, (arylH's); delta 7.01, d, 2H (arylH's); delta 2.65, t, 2H, (CH2 alpha to aryl); delta 2.38, t, 2H (CH2 alpha to COOH); delta 1.13, s, 9H (t-Bu). 13C NMR (d6- DMSO): 174, 148, 137, 127.8, 125.9, 35, 33, 31.2, 29.5.Compound 10a (3.81g, 0.02mol) was dissolved in dry benzene (5mL, 0.06mol) at room temperature then SOCl2 (10mL, 0.14mol) was added in a dropwise manner. The reaction mixture was heated at reflux for 15h. The solvent was evaporated under reduced pressure to give 11a (4.49g, 95%) as a yellow oil. The crude product was used in the next step without further purification or characterization.3-(4-t-Butylphenyl)propionyl Chloride A 2 L 3 neck round bottom flask fit with a condenser, thermometer, nitrogen inlet, and overhead stirrer was charged with 3-(4-t-butylphenyl)propionic acid (118.7 g, 0.576 mol), thionyl chloride (210 mL, 2.88 mol), dimethylformamide (3 drops), and methylene chloride solvent. The reaction was refluxed for 3 hours and additional 3-(4-t-butylphenyl)propionic acid (8.17 g, 0.040 mol) was added to the reactor and refluxed for an additional hour. After allowing to stand overnight, the reaction was stripped of volatiles to yield the crude 3-(4-t-butylphenyl)propionyl chloride (99.0 g).1H-NMR (CDCl3, 500 MHz) delta 7.33 (d, JAB=8 Hz, 2H); 7.12 (d, JAB=8 Hz, 2H); 3.20 (t, J=7.5 Hz, 2H); 2.98 (t, J=7.5, 2H); 1.31 (s, 9H).EXAMPLE 8; 3-(4-tert-butyl-phenyl)-N-[6-(2-hydroxy-phenyl)-5-methyl-pyridin-3-yl]-propionamide (Cpd 160) A. To Cpd 1b (3.42 g, 16.6 mmol) was added 15 mL thionyl chloride (15 mL, 206 mmol). The solution was heated at reflux for 2 h. The reaction was evaporated in vacuo, dissolved in benzene and evaporated, and the process was repeated. Compound 8a (3.67 g, 16.3 mmol) was obtained as a light yellow liquid and used for subsequent reactions without further purification.EXAMPLE 24; 3-(4-tert-Butyl-phenyl)-N-[4-(4, 5-dichloro-imidazol-1-yl)-3-trifluoromethyl-phenyl]-propionamide (Cpd 212) A. A solution of 3-(4-tert-butyl-phenyl)-propionic acid (Cpd 24a, 0.518 g, 2.51 mmol) in 10 mL SOCl2 was heated at reflux for 2.5 hours. The reaction mixture was evaporated in vacuo, treated with benzene, and evaporated again to yield compound 24b as a yellow-orange oil.Carbonylation2 reactions were carried out in a 50 mL Parr autoclave reactor made of Hastelloy C-276 material following a procedure similar to that described previously [8]. For a typical reaction, the solid catalyst and the liquid phase reactants/solvent were charged in the reactor and sealed. The contents were heated to the desired temperature, then CO gas was introduced to the reactor to the desired pressure and the reaction started by switching on the stirring. The consumed CO was made up from a reservoir through a constant pressure regulator. The progress of the reaction was followed by observing the pressure drop in a CO reservoir as a function of time and the reaction was stopped at completion of CO absorption. Afterwards, the reactor was brought to ambient temperature, its content-gas was released and flushed thrice with N2 and liquid phase samples were analyzed for reactant/products composition using HP GC 6890 fitted with a HP-FFAP capillary column (25 m × 0.33 mm × 0.2 mum). GC-MS analyses of the samples were performed using Agilent 5973 N Mass Selective Detector attachment.General procedure: Olefins hydrocarboxylation catalyzed by Pd-TPPTS/LSI-600 in supported aqueous phase were performed in a 50ml stainless-steel autoclave. In a standard procedure, 0.22%Pd-TPPTS/LSI-600cata-lyst 1.5g, deoxygenated water(1.0g, 55.6mmol), 1-hexene(0.5g, 6.0 mmol)(n-undecane was used as internalstandard for GCanal-ysis) were added into the autoclave, then the reactor was sealed and flushed three times with10atm of CO.After that, the reactor was transferred into oil-bath, heated to the desired temperature(120 C) and stirred for 6h.Upon reaction completion, theauto-clave wascooledwithice-water to room temperature and thenvented slowly.The organic products and un-reacted olefins were extracted with3×2mlofheptane.The combined organic phase was dried by MgSO4 and then used tobe analyzed by GC andGC-MS. The solid catalyst was filtrated and then washed with3× 2mlof heptane, followed by drying the catalystat75 C for 5h undervacuum condition.A fresh charge of reactants was introduced and the reaction was carried out as described previously.The hydro-carboxylation of styrene derivatives were carriedout insimilar procedures except for 2ml of heptane was added as organic solvent during the reaction.Under a nitrogen atmosphere, palladium sulfate (1mo1%, 2.0mg), Tris (3-chlorophenyl) phosphine (3 mol%, 10.9 mg), Iron p-toluenesulfonate (2 mol%, 11.4 mg) and magnetons were added to a 5 mL glass tube. N-methylpyrrolidone (2 mL) was subsequently added, 4-tert-butylstyrene (1 mmol, 160 mg), Distilled water (2 mmol, 36 mg). Place the reaction tube in the reaction kettle, seal the reaction kettle, remove the air in the reaction kettle and wash it with carbon monoxide three times, and finally pressurize the carbon monoxide to 30 bar. After the addition was completed, the reaction kettle was placed in a metal module preheated to 100 degrees Celsius in advance and stirred for 20 hours. After the reaction is completed, the reaction system is cooled to room temperature and the pressure is slowly released. Using dodecane as an internal standard, the yield of 92% was determined by the working curve of gas chromatography, and the branched / straight chain was '6/94.3-(4-t-Butylphenyl)propionic Acid A 3 L autoclave was charged with wet t-butylcinnamic acid (248 g, 1.21 mol), tetrahydrofuran (1 L), and ethanol (1 L) and palladium on carbon (35 g). The reactor was shut and 90 psi of hydrogen pressure applied and the reactor held at room temperature overnight. The reaction was then transferred to a round bottom flask and concentrated to 200 mL. The formed crystals were decanted and washed with hexane to give 3-(4-t-butylphenyl)propionic acid (52.9 g after vacuum drying). A second crop from the filtrate yielded additional 3-(4-t-butylphenyl)propionic acid (65.8 g).

Molecular Weight:206.28
XLogP3:3.5
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:4
Exact Mass:206.130679813
Monoisotopic Mass:206.130679813
Topological Polar Surface Area:37.3
Heavy Atom Count:15
Complexity:207
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes