To a RB flask equipped with magnetic stirring bar, condenser, thermometer, Dean-Stark trap, and N2 inlet and bubbIer was added benzo[b]naphtho[2,1-d-]-thiophene-5-carbaldehyde (SISA Pharmaceutical Laboratories, Inc., 763 Concord Ave., Cambridge, Mass., 02138, 4.94 g, 18.83 mmol), 2-amino-2-methyl-1,3-propanediol (Aldrich, 1.98 g, 18.83 mmol), p-toluenesulfonic acid monohydrate (Aldrich, 0.1 g) and PhCH3 (200 mL). The mixture was stirred at reflux with removal of H2O for 2.5 h (or until no H2O is collected). Most of the PhCH3 was then removed by distillation. The mixture was then cooled in an ice bath and diluted with abs. EtOH (200 mL) and further cooled. Solid NaBH4 (MCB Manufacturing Chemists, Inc., 2909 Highland Ave., Cincinnati, Ohio, 45212, 0.712 g, 18.83 mmol) was added in one portion to the reaction mixture. The ice bath was then removed, the reaction mixture allowed to warm to RT and stirred overnight. The reaction was then acidified with 10% HCl and the solvents removed by rotary evaporation. The crude solid was shaken with 1N HCl (300 mL) filtered, washed with 1N HCl (300 mL), sucked semidry, and washed with Et2O (300 mL). The material was dissolved in CH3OH (200 mL), filtered and basified with 1N NaOH solution (1 L). A white solid formed which was extracted with EtOAc (3×500 mL). The EtOAc washings were combined, filtered, washed with saturated NaCl (3×500 mL), dried with K2CO3 (Mallinckrodt, 25 g) filtered, and concentrated by rotary evaporation to give a white solid. This was dissolved in a mixture of abs. EtOH (200 mL) and CH3SO3H (99.5%, Morton Thiokol, Inc. - Alfa Products, P.O. Box 299, 152 Andover St., Danvers, Mass., 01923, 3 mL), filtered and diluted to 4 L with a mixture of Et2O/hexane (1:1). This material was recrystallized three times from EtOH/hexane (1:3) to give 2-[(benzo-[b]naphtho[2,1-d]thiophen-5-ylmethyl)amino]-2-methyl-1,3-propanediol methanesulfonate, mp 221°-222° (C,H,N.,S).
