The general procedure for the synthesis of Cbz-β-alanine methyl ester from benzyl bromide is as follows:
Example 22 Synthesis of STR94N-CBZ-β-alanine methyl ester: The target compound was prepared by the reaction of N-CBZ-β-alanine (5 g, 22.4 mmol), methanol and thionyl chloride according to the method described in Step A of Example 1.
Synthesis of STR95: To a stirred solution of the intermediate (330 mg) from the previous step in THF (3 mL) was added potassium bis(trimethylmethylsilyl) amide (3 mL, 0.5 M in toluene) followed by hexamethylphosphoramidite (5 mL) at -78 °C. The mixture was slowly warmed to room temperature and after forming a clarified solution, it was cooled again to -78°C. To this solution was added another portion of potassium bis(trimethylmethylsilyl)amide (3 mL, 0.5 M solution in toluene). After 1 hour of reaction at -78 °C, benzyl bromide (193 μL) was added to the reaction mixture. The solution was continued to be stirred at -78 °C for 3 h. Subsequently, it was poured into 0.5 N HCl and extracted three times with ether. The combined organic layers were washed sequentially with water (5 times) and brine, dried with magnesium sulfate and concentrated. The residue was purified by preparative thin layer chromatography (Pre-TLC, unfolding agent ratio hexane/ethyl acetate = 4/1) to afford the target compound (164 mg, 35% yield).
