Hydrochloric Acid → T-817 maleate

Participants

Reaction Conditions

Reaction Steps

To tetrahydrofuran (3 mL) suspension of 0.50 g of 1-(3-(2-(1-benzothiophen-5-yl)ethoxy)propionyl)azetidin-3-ol was added 0.19 g of sodium borohydride, which was then heated to 50° C. Thereto was dropwise added tetrahydrofuran (1 mL) solution of 0.46 mL of dimethyl sulfate at 50 to 55° C. for 10 minutes, which was then stirred at same temperature for 2.5 hours. After cooling, thereto was dropwise added 1.64 mL of 6.0 mol/L hydrochloric acid, which was then refluxed for 1.5 hours. To the reaction mixture was added ethyl acetate, and the pH was adjusted to 10.0 with 20% (w/w) sodium hydroxide aqueous solution. The organic layer was separated, washed sequentially with water and saturated sodium chloride aqueous solution, and dried over anhydrous magnesium sulfate. After insoluble matter was filtered off, the solvent was distilled off under reduced pressure. To the resultant residue was added 0.18 g of maleic acid, which was solidified from a mixed solvent (3.75 mL) of ethyl acetate:2-propanol (4:1) to provide 0.49 g of 1-(3-(2-(1-benzothiophen-5-yl)ethoxy)propyl)azetidin-3-ol maleate as colorless crystal form.

Provenance & Evidence