Hydrochloric Acid → HCID 86691522, compound

Participants

Reaction Conditions

Reaction Steps

A solution of R-16 (9.0 mmol, 2.6 g) is dissolved in MeOH (24 mL) and cooled to 0° C. Sodium borohydride (9.0 mmol, 0.34 g) is added slowly to the mixture and the reaction is stirred at room temperature for 3 h. The mixture is concentrated under reduced pressure and the residue is diluted with DCM and water. The organic layer is separated, washed with brine, dried over Na2SO4, and concentrated under reduced pressure. The residue is purified using flash silica gel chromatography to provide R-17 (0.26 g, 100%). To a solution of R-17 (0.91 mmol, 0.26 g) in THF (5 mL) is added TEA (0.14 ml, 1.0 mmol) followed by methanesulfonyl chloride (1.0 mmol, 0.078 ml). The reaction mixture is allowed to stir at room temperature for 16 h. To the mixture is added DBU (1.8 mmol, 0.27 m) and the reaction is allowed to stir at room temperature for 2 h. The mixture is diluted with EtOAc and washed sequentially with a saturated aqueous solution of NH4Cl followed by a 1M solution of HCl. The organic phase is dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue is purified by flash silica gel chromatography to provide R-18 (0.26 g, 100%). To a solution of trimethylsulfoxonium iodide (1.0 mmol, 0.23 g) in DMSO (24 mL) is slowly added NaH (60% dispersion in mineral oil, 1.0 mmol, 0.042 g). The mixture is stirred at room temperature for 1 h and then a solution of R-18 (0.950 mmol, 0.26 g) in DMSO (0.5 mL) is rapidly added. The reaction mixture is heated to 50° C. for 2 h and then cooled to ambient temperature and stirred for 16 h. The reaction mixture is diluted with water and extracted with ethyl acetate. The combined organic phase is washed with brine then dried over anhydrous sodium sulfate and concentrated under reduced pressure to provide R-19 (0.17 g, 63%). To a solution of R-19 (0.60 mmol, 0.17 g) in a 3:1 mixture of Et2O:DCM (4 ml) is added a solution of HCl in 1,4-dioxane (4M, 4 mmol, 1.0 mL). The mixture is stirred at 45° C. for 3 h then concentrated under reduced pressure. The residue is washed with Et2O and dried to provide the title compound (0.099 g, 75%).

Provenance & Evidence