(ETHYLTHIO)ACETIC ACID

1) To a stirred solution of sodium alkanethiolate (32) (1 eq) in anhydrous DMF (10 mL) at 0 C was added bromoalkyl carboxylate (31) (1 eq) over 5 min. The reaction mixture was stirred at room temperature for 15 hours. The reaction progress was monitored by thin layer chromatography (TLC). The reaction mixture was diluted with ethyl acetate (20 mL) and washed with saturated NaHCO3 solution (aqueous layer was quenched with bleach). The organic layer was dried with anhydrous Na2SO4 to afford the corresponding alkylthioether carboxylate (33), which was purified by silica gel column chromatography using a gradient of hexane and ethyl acetate and separated as a colorless oil.

2) To a stirred solution of ethyl thioether ether carboxylate (33) (0.1 mol, 1 eq.) in ethanol (20 mL) was added a 2N aqueous solution. NaOH (1.5 eq.) was added dropwise to the reaction mixture. The reaction mixture was stirred at room temperature for 30 minutes (the progress of the reaction was monitored by TLC). After completion of the reaction, the reaction mixture was concentrated on a rotary evaporator and the residue was cooled in an ice bath. Several pieces of crushed ice were introduced into the flask and neutralized with 1NHCl. The product was extracted with ethyl acetate (20 x 20 mL). The combined extracts were dried over Na2SO4 and evaporated at 0 C on a rotary evaporator. The residue was purified by silica gel column chromatography using hexane as eluent to give pure (ethylthio)acetic acid (14).