2-Hydroxyethyl Methanethiosulfonate synthesis

Yield:-

Reaction Conditions:

in ethanol; for 7 h;Heating / reflux;

Steps:

4

EXAMPLE 4; Synthesis of (Z) -5-Fluoro-2-methyl-1- [ [4- (methylsulfinyl) phenyl] methylene] -IH-indene-3 -acetic acid 2-methanesulfonylsulfanylethyl ester; Sodium sulphide nonahydrate (4 g; 16.32 mmol) is EPO suspended in 12 ml of anhydrous ethanol at -15⁰C. To this suspension is added dropwise a solution of methansolfochloride (1.4 ml, 17.96 mmol) in 3.2 ml of anhydrous ethanol . After complete addition the suspension is kept overnight under stirring. The mixture of reaction is filtered and the solution evaporated to dryness.Pure sodium methanthiosulfonate is obtained after crystallization of the residue by ethanol. The sodium methanthiosulfonate (690 mg, 5.14 mmol) is suspended in ethanol and 2-bromoethanol (0.76 ml, 10.28 mmol) is then added dropwise to the suspension. After the complete addition the reaction mixture is refluxed for 7 hours . After cooling, the product is filtered to remove NaBr. The ethanol solution is evaporated, and the residue is dissolved in CHCl₃ and extracted with water. The aqueous solution is evaporated to dryness, tetrahydrofuran (THF) is added to the residue and the obtained suspension is filtered.The THF solution is evaporated to obtain a pale yellowish oil (methanethiosulfonic acid S- (2- hydroxyethyl) ester, HEMTS) . HEMTS (400 mg, 2.56 mmol), sulindac sulfone (912 mg, 2.56 mmol) and dimethylaminopyridine (DMAP) (15 mg) are added to a IN solution of EPO dicyclohexhylcarbodiimide (DCC) in methylene chloride (2.6 ml) . The reaction is stirred at room temperature, under nitrogen for 1.5 hours. The mixture is filtered, and the dichloromethane solution is extracted with IN HCl, water, saturated solution of sodium bicarbonate and water. After evaporation of the solvent the residue was chromatographed on a silica gel column, eluting with dichloromethane containing 0.5% of methanol. The compound has a melting point of 118.5-119.5 ⁰C.

References:

WO2006/134489,2006,A1 Location in patent:Page/Page column 15-17