4-Methyl-γ-oxobenzenebutanoic acid

White to light beige crystalline powder

Dissolve 75.7 g of succinic anhydride in 457.5 ml of toluene.220.5 g of anhydrous AlCl3 are added batchwise. The reaction mixture is controlled at a temperature of 50-60°C.After stirring for 2 hours, The end of the reaction was confirmed by TLC. With vigorous stirring, The reaction solution was slowly added dropwise to 1250 ml of 1 mol/L ice hydrochloric acid.Gradually precipitated milky solids, After the addition was complete, the mixture was stirred for 0.5 hours and filtered.After the filter cake was washed with toluene and ice water, Withdrawing the filter cake with 50 ml of ethyl acetate;Slowly add the solution and add 500ml of petroleum ether to crystallize.After stirring for another 0.5 hours, Filter and dry at 40°C for 2 hours to obtain Compound II144g.Yield 99.3percent.[Compound II intermediate] white solid, General procedure: The general procedure (Scheme 1) for the preparation of compounds (2a, 2b and 2c): succinicanhydride (1 equiv, 10 mmol) was reacted with an appropriate aromatic compound (substitutedbenzene, 1 equiv, 10 mmol) in DCM (20 mL) in the presence of anhydrous aluminium chloride(1.5 equiv, 15 mmol). The reaction mixture was stirred under anhydrous conditions overnight at roomtemperature and then ice-cold diluted hydrochloric acid solution was added dropwise. A solid massseparated out which was filtered and purified by recrystallization to give 2a, 2b and 2c [44].General procedure: AlCl3 (1.0 g, 7.5 mmol)was added portion-wise to a solution of succinic anhydride (0.5 g, 5 mmol) and anaromatic compound (6 mmol) in CH2Cl2 (5 mL) at room temperature. The mixture wasstirred at room temperature for overnight, and the mixture was poured into 1N HClsolution (10 mL), extracted with ethyl acetate (15 mL x 3). The organic layer was driedover MgSO4. The solvent was removed under reduced pressure, and the crude productwas purified by recrystallized from ethyl acetate and hexane.To a suspension of succinic anhydride (1 g, 10.2 mmol, 1 eq)in toluene (4.6 mL, 44.8 mmol, 4.4 eq) kept at 0 C, aluminumchloride (2.7 g, 20.4 mmol, 2 eq) was added in small portions.The resulting suspension was stirred at room temperature for3 h, then poured onto ice and acidified with HCl conc. The aqueoussolution was extracted with EtOAc and the combined organiclayers were dried (Na2SO4) and concentrated under reducedpressure. The residue was triturated with petroleum ether to furnish4 as a white solid (1.35 g, 69percent). Rf = 0.36 (petroleum ether/EtOAc 4:6), mp 125–128 C; 1H NMR (400 MHz, Chloroform-d) d7.88 (d, J = 8.0 Hz, 2H), 7.26 (d, J = 8.0 Hz, 2H), 3.29 (t, J = 6.6 Hz, 2H), 3.00 (br s, 1H, OH, exch. with D2O), 2.80 (t, J = 6.0 Hz, 2H), 2.41 (s, 3H).

Molecular Weight:192.21
XLogP3:1.9
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:4
Exact Mass:192.078644241
Monoisotopic Mass:192.078644241
Topological Polar Surface Area:54.4
Heavy Atom Count:14
Complexity:215
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes