4-(4-BROMOPHENYL)BUTANOIC ACID

Zinc (13.0 g, 200 mmol) and mercury chloride (1 .00 g, 480 mmol) were stirred with water (10 mL) and concentrated HCI (0.6 mL) for five minutes. The liquid was decanted off and toluene (20 mL), concentrated HCI (20 mL) and water (8 mL) were added consecutively. 4-(4-bromophenyl)-4-oxobutanoic acid 4 (2.55 g, 10.5 mmol) was added and heated under reflux at 100°C for 24 h adding HCI (1 mL) every 6 h. The reaction was allowed to cool to room temperature, filtered and the solvent removed from the organic layer to give a clear liquid which gave white crystals upon cooling. These were purified with silica gel chromatography (ethyl acetate : hexane, 1 :3) to yield 4-(4- bromophenyl)butanoic acid 5 (2.33 g, 9.63 mmol, 91 .4percent). MS (ESI-QUADRUPOLE) m/z: calc. for CioHn BrO3-(4-Bromobenzoyl)propionic acid (5.142 g, 20 mmols) and potassium hydroxide (2.693 g, 48 mmols) were placed in a round-bottomed flask fitted with a condenser and a Dean-Stark apparatus and suspended in diethylene glycol (50 mL) at room temperature. Hydrazine (1.508 mL, 48 mmol) was slowly added to the reaction which was subsequently heated to 120-130 °C for 2 h upon which the reaction became homogenous. After 2 h, the temperature was increased to 180-200 °C and stirring was continued for 3 h in order to distill off the remaining hydrazine and water byproduct via the Dean-Stark trap. Then, the reaction was allowed to cool to room temperature, diluted with water (20 mL), and carefully poured into 2.5 M hydrochloric acid (40 mL). The precipitate that formed was collected by filtration and residual diethylene glycol was removed by dissolving the precipitate in a saturated, aqueous solution of potassium carbonate (40 mL). This solution was diluted with water (40 mL) and carefully poured into 2.5 M hydrochloric acid (40 mL). A white precipitate formed which was collected by filtration, washed with water (2 x 30 mL), and dried under vacuum to yield the desired product as a white solid (886 mg, 89percent). Step B: A mixture of the product from Step A (57 g, 223 mmol), potassium hydroxide (43 g, 760 mmol) and hydrazine hydrate (26 ml, 830 mmol) in diethylene glycol (2865 ml) was stirred at 195° C. for 3 hours. After cooling below 40° C., the mixture was diluted with water (300 ml), poured into 3 M NaOH and washed with dichloromethane three times. Brine was added to break up the emulsion. The aqueous layer was acidified to pH 1 with 6 M HCl and extracted with methyl tert-butyl ether three times. The combined organic extracts were dried over magnesium sulfate to give 4-(4-bromophenyl)butyric acid (41 g, 75percent):

Molecular Weight:243.10
XLogP3:3
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:4
Exact Mass:241.99424
Monoisotopic Mass:241.99424
Topological Polar Surface Area:37.3
Heavy Atom Count:13
Complexity:162
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes