4-Bromo-γ-oxobenzenebutanoic acid

white to light beige shiny crystalline flakes

Succinic anhydride 3 (5.0 g, 50 mmol) and bromobenzene 2 (48 g, 300 mmol) were cooled to 0°C. Aluminium chloride (13.3 g, 100 mmol) was added and the mixture was stirred for 4 h at 0°C under nitrogen atmosphere. The reaction was allowed to warm to room temperature and stirred for 96 h under nitrogen atmosphere. The reaction was cooled to 0°C and concentrated HCI (125 mL) was added and reaction stirred under nitrogen for a further 1 h. The reaction was filtered and washed with water (1 L) to obtain a pale yellow solid which was recrystallised from toluene to yield 4-(4- bromophenyl)-4-oxobutanoic acid 4 (12 g, 46.68 mmol, 93.4percent). MS (ESI-QUADRUPOLE) m/z: calc. for CiStep 1: Synthesis of 4-(4-bromophenyl)-4-oxobutanoic acid (37A, R═Br) (0320) Anhydrous aluminum trichloride (29.1 g, 218 mmol) was suspended in dichloromethane (120 mL) and cooled to 0° C. Bromobenzene (35.1 g, 224 mmol) was added carefully. When the addition was complete, succinic anhydride (10.0 g, 100 mmol) was added in ten portions carefully. Then the mixture was warmed to room temperature and stirred for 4 h. TLC showed the reaction was complete, 6N HCl (50 mL) was added dropwise. The solid was filtered, washed with distilled water (10 mL×2) and dried in vacuo to afford 37A, R═Br as a white solid (22 g, yield 82percent).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.Step A: Bromobenzene (150 ml, 1.42 mol) was added in one portion to a mixture of aluminum chloride (109 g, 0.82 mmol) and succinic anhydride (41 g, 0.41 mol) in cyclohexane (200 ml) at 80° C. and the resulting mixture was stirred at 80° C. for 2 hours. After cooling below 40° C., the mixture was slowly poured into 6 M HCl (200 ml) and ice, and yellow solids precipitated. Methyl tert-butyl ether was added to dissolve the solids and the phases were separated. The organic layer was washed with water three times and was extracted into 2 M NaOH. The aqueous extracts were acidified to pH 1 with 6 M HCl, extracted with methyl tert-butyl ether, dried with magnesium sulfate and concentrated to a residue. This material was recrystallized by dissolving the residue in 50:35:15 cyclohexane/toluene/isopropanol at 70° C. followed by cooling to room temperature, filtering and azeotroping the resulting solids with hexanes to give the desired compound (57 g, 55percent) as a white solid:

Molecular Weight:257.08
XLogP3:2.1
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:4
Exact Mass:255.97351
Monoisotopic Mass:255.97351
Topological Polar Surface Area:54.4
Heavy Atom Count:14
Complexity:219
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes