Synthesis
(1) Synthesis of 4-benzyloxybutyric acid: 4.0 g (60%, 0.1 mol) of sodium hydride was washed in hexane and mixed with 30 mL of anhydrous DMSO, the resulting mixture was stirred at 60°C in an oil bath for 1 hour. The mixture was cooled to room temperature under nitrogen protection and 100 mL of dry DMSO solution containing 12.6 g (0.1 mol) of sodium 4-hydroxybutyrate was added. After stirring for 2 hours at room temperature, the reaction solution was cooled in an ice bath, 0.2 mol of benzyl bromide was added slowly and the reaction continued for 2 hours at room temperature. After completion of the reaction, 0.5 L of ether was added, the mixture was filtered, the residue was washed with ether (300 mL x 3) and the filtrate was concentrated in vacuum. The concentrated residue was mixed with 100 mL of methanol, 100 mL of 8% sodium hydroxide solution was added, and the mixture was stirred at 60°C for 15 hours. After vacuum drying, the concentrated residue was washed with ether (200 mL x 2) and the ether layer was extracted with 1N sodium hydroxide (50 mL). All aqueous layers were combined and the pH was adjusted to <4 with concentrated hydrochloric acid and then extracted with ether (100 mL x 5). The ether layer was then extracted with 2N sodium hydroxide (50 mL x 3) and all aqueous layers were again neutralized with concentrated hydrochloric acid to pH <4 and extracted with ether. The resulting product was washed with saturated aqueous sodium chloride, dried over magnesium sulfate and concentrated in vacuum to give 9.42 g of 4-benzyloxybutyric acid as a light yellow oil in 49.5% yield.NMR (500 MHz, CDCl3): δ 1.95 (2H, dt, J = 6 and 7 Hz, β-CH2), 2.50 (2H, t, J = 7 Hz, α-CH2), 3.54 (2H, t, J = 6 Hz, γ-CH2), 4.52 (2H, s, PhCH2O), 7.25-7.4 (5H, m, C6H5), 10.0-10.8 (1H, br, CO2H); IR (pure): ν 1710 cm-1 (COOH); FAB-MS: m/z = 195 (M + H+).
