1-Hydroxybenzotriazole → Rac.-n-[2-chloro-4-[3-(3-hydroxyphenyl)-1-oxopropan-1-yl]benzoyl]-2-(dimethoxyphosphinyl)glycine methyl ester

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Reaction Steps

Diisopropylethylamine (1.05 mL, 6 mmol) was added to a solution of 2-chloro-4-[3-(3-hydroxyphenyl)-1-oxopropan-1-yl]benzoic acid (Example 94; 457 mg, 1.5 mmol), rac.-2-(dimethoxyphosphinyl)glycine methyl ester (Example 125) freshly prepared from rac.-N-(benzyloxycarbonyl)-2-(dimethoxyphosphinyl)glycine methyl ester (662.5 mg, 2.0 mmol), O-(benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (597 mg, 1.6 mmol) and 1-hydroxybenzotriazole (223 mg, 1.65 mmol) in N,N-dimethylformamide (12 mL). The solution was stirred at room temperature for 17 h and then it was evaporated in vacuo to remove N,N-dimethylformamide. A solution of the residue in ethyl acetate (40 mL) was washed in turn with 0.5N hydrochloric acid solution (20 mL), brine (20 mL), saturated sodium bicarbonate solution (20 mL) and brine (20 mL). Each of the aqueous layers was extracted with ethyl acetate (20 mL). The combined organic layers were dried (Na2SO4), filtered and evaporated under reduced pressure. The resulting oil was chromatographed over silica gel (75% ethyl acetate/hexanes, then 5% methanol/ethyl acetate) to give rac.-N-[2-chloro-4-[3-(3-hydroxyphenyl)-1-oxopropan-1-yl]benzoyl]-2-(dimethoxyphosphinyl)glycine methyl ester (450 mg, 62% yield) as an oil.

Provenance & Evidence