Lithium Hydroxide → HCID 59199322, compound

Participants

Reaction Steps

To a solution of 1-bromomethyl-3-iodo-benzene (CAS#49617-83-6, 25.0 g, 84 mmol) in acetone (500 mL) is added mercapto-acetic acid methyl ester (9.0 g, 85 mmol) followed by K2CO3 (15.2 g 110 mmol). The reaction is permitted to stir overnight. The next morning the reaction is filtered and concentrated. The resulting residue containing (3-iodo-benzylsulfanyl)-acetic acid methyl ester is then dissolved in methanol (300 mL). The methanol solution is charged with water (100 mL) and lithium hydroxide (6.0 g, 252 mmol). The reaction is permitted to stir at room temperature until the starting ester is consumed as determined by TLC analysis. The reaction is then brought to a pH<4 by the addition of 3N aqueous HCl. The reaction is then concentrated to approximately ¾ of its original volume and diluted with ethyl acetate. The layers are separated and the organic layer is dried with Na2SO4, filtered and concentrated to afford a residue containing 3-iodo-benzylsulfanyl)-acetic acid. The residue is dissolved in chlorobenzene (500 mL) and treated with P2O5 (64 g, 450 mmol). The reaction is heated at reflux overnight. The reaction is then cooled to room temperature and filtered. The eluent is then concentrated to dryness. The resulting residue is dissolved in ethyl acetate and washed with brine. The organic layer is then dried with Na2SO4, filtered, and concentrated. The resulting residue is purified by silica gel flash chromatography (ethyl acetate-hexanes, 0:1 to 1:5) to afford 7-iodo-isothiochroman-4-one; MS: (ESI) m/z 308.0 (M+NH4)+

Provenance & Evidence