Hydrochloric Acid → T-817 maleate

Participants

Reaction Conditions

Reaction Steps

To bis(2-methoxyethyl)ether (5 mL) suspension of 1.00 g of 1-(3-(2-(1-benzothiophen-5-yl)ethoxy)propionyl)azetidin-3-ol was added 0.37 g of sodium borohydride, which was then cooled to 10° C. Thereto was dropwise added 2.49 mL of chlorotrimethylsilane at 5 to 10° C. for 20 minutes, which was then stirred at room temperature for 2.5 h and at 40° C. for 4 hours. After cooling, thereto was dropwise added 3.27 mL of 6.0 mol/L hydrochloric acid, which was then stirred at 70 to 75° C. for 30 minutes. To the reaction mixture were added water and ethyl acetate, and the pH was adjusted to 10.0 with 2.0 mol/L sodium hydroxide aqueous solution. The organic layer was separated, washed sequentially with water and saturated sodium chloride aqueous solution. Thereto were added anhydrous magnesium sulfate and activated carbon. After insoluble matter was filtered off, the solvent was distilled off under reduced pressure. To the resultant residue was added 0.36 g of maleic acid, which was solidified from a mixed solvent (5 mL) of ethyl acetate:2-propanol (4:1) to provide 0.72 g of 1-(3-(2-(1-benzothiophen-5-yl)ethoxy)propyl)azetidin-3-ol maleate as colorless crystal form.

Provenance & Evidence