1-(4-BROMOPHENYL)CYCLOPROPANECARBOXYLIC ACID

A mixture of compound XV-2 (7.5 g, 33.78 mmol), KOH (7.6 g, 135 mmol) and ethylene glycol (50 mL) were heated to 160°C for 6 hrs. The mixture was cooled to room temperature, water (200 mL) was added and the mixture was acidified to pH=3~4 with aq. HCl (2 N) to precipitate the product. The product was collected by filtration to yield compound XV- 3 (5.6 g, yield 69percent). MS (ESI) m/z (M+H)Step 2: A solution of 4-bromophenylacetonitrile (50.0 g, 255 mmol), 1-bromo-2-chloroethane (26.5 mL, 319 mmol), benzyltriethylammonium chloride (1.16 g, 5.10 mol), and potassium hydroxide (100 g, 1.79 mol) in water (100 mL) was stirred at 50°C for 3 h. Ethanol (400 mL) was added to the reaction mixture, and the mixture was stirred at 100°C for 3 days. The reaction mixture was neutralized by pouring it into 5 N hydrochloric acid (360 mL) with ice cooling. The reaction mixture was extracted with dichloromethane, the organic layer was dried with anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure. Diisopropyl ether was added to the residue, and the precipitate was collected by filtration and dried under reduced pressure to obtain the title compound (50.4 g, 82percent) as a white solid. Step 1 : Preparation of l-(4-bromophenyl)cyclopropanecarboxylic acid To a mixture of 4-bromophenylacetonitrile (5.0 g, 25.44 mmol) and benzyltriethylammonium chloride (144.9 mg, 0.63 mmol) was added 1, 2-dibromoethane (7.45 mL, 86.5 mmol). The reaction mixture was heated to 70 °C followed by dropwise addition of 50percent aqueous sodium hydroxide solution (25 mL). The reaction mixture was heated at 70 °C for 7 h and then heated at 150 °C for 15 h. After the completion of reaction as confirmed by TLC, the reaction mixture was diluted with diethyl ether ( 100 mL). The aqueous layer was separated and acidified with 50percent aqueous HCl to pH 1. The crude compound was diluted with ethyl acetate (500 mL). The organic layer was separated, washed with water (2 x 10 mL), dried over NaStep 1: A sealed tube was charged with 1-phenyl cyclopropane carboxylic acid (3.0 g, 18.5mmol), sodium acetate (1.75 g, 1.1 eq) and glacial acetic acid (10 mL). To the stirredsolution at 15 00, Br2 (1 .2 mL, 1 .0 eq) was added under nitrogen atmosphere. Then, the reaction mixture was stirred at room temperature for 15 mm and gradually raised the temperature to 55 00 and maintained the same for another 48 h. The reaction mixture was quenched with ice water and extracted with ethyl acetate. The organiclayer was washed with water and brine solution and then wasdried and concentrated. The obtained product was triturated with n-hexane to yield the title compound (3.34 g, 75.14percent) as a pale yellowish solid.