1-Hydroxybenzotriazole → N-[2-chloro-4-[1-hydroxy-3-(3-hydroxyphenyl)propan-1-yl]benzoyl]-2-(dimethoxyphosphinyl)glycine methyl ester

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Reaction Steps

Diisopropylethylamine (0.61 mL, 3.5 mmol) was added to a solution of rac.-2-chloro-4-[1-hydroxy-3-(3-hydroxyphenyl)propan-1-yl]benzoic acid (Example 96; 270 mg, 0.88 mmol), rac.-2-(dimethoxyphosphinyl)glycine methyl ester (Example 125) freshly prepared from rac.-N-(benzyloxycarbonyl)-2-(dimethoxyphosphinyl)glycine methyl ester (397 mg, 1.2 mmol) ), O-(benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (350 mg, 0.97 mmol) and 1-hydroxybenzotriazole (131 mg, 0.97 mmol) in N,N-dimethylformamide (7 mL). The solution was stirred at room temperature for 17 h and then it was concentrated under high vacuum to remove N,N-dimethylformamide. Ethyl acetate (25 mL) was added and the solution was washed in turn with 0.5N hydrochloric acid solution (10 mL), brine (10 mL), saturated sodium bicarbonate solution (10 mL) and brine. Each of the aqueous layers was back-washed in turn with ethyl acetate (10 mL). The combined organic layers were dried (MgSO4), filtered, evaporated and the resulting residue was chromatographed over silica gel (50-100% ethyl acetate/hexanes, then 5% methanol/ethyl acetate) to flirnish N-[2-chloro-4-[1-hydroxy-3-(3-hydroxyphenyl)propan-1-yl]benzoyl]-2-(dimethoxyphosphinyl)glycine methyl ester (260 mg, 61% yield) as a colorless oil.

Provenance & Evidence