1-Hydroxybenzotriazole → Rac.-n-[2-chloro-4-[[[(1h-indol-6-yl)methyl]amino]carbonyl]benzoyl]-2-(dimethoxyphosphinyl)glycine methyl ester

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Reaction Steps

O-(benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (2.4 g, 6.4 mmol) was added to a solution of 2-chloro-4-[[[(1H-indol-6-yl)methyl]amino]carbonyl]benzoic acid (Example 117; 1.9 g, 5.8 mmol) and rac.-2-(dimethoxyphosphinyl)glycine methyl ester (Example 125; 2.10 g, 10.6 mmol) in N,N-dimethylformamide (20 mL). 1-hydroxybenzotriazole (861 mg, 6.4 mmol) was then added, followed by diisopropylethylamine (2 mL, 11.6 mmol). The solution was stirred overnight at room temperature and then it was concentrated under high vacuum to remove N,N-dimethylformamide. The residue was partitioned between water and ethyl acetate and the separated organic phase was washed in turn with cold 1N hydrochloric acid solution, cold saturated sodium bicarbonate solution and brine, then was dried (MgSO4), filtered and evaporated in vacuo. The crude product was chromatographed over silica gel (0-4% methanol/dichloromethane) to give rac.-N-[2-chloro-4-[[[(1H-indol-6-yl)methyl]amino]carbonyl]benzoyl]-2-(dimethoxyphosphinyl)glycine methyl ester (2.1 g, 72% yield) which was used in subsequent reactions without further purification.

Provenance & Evidence