反应详情

O-(Benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (645 mg, 1.7 mmol) was added to a solution of 2-chloro-4-[[(3-hydroxybenzyl)amino]carbonyl]-6-methylbenzoic acid (Example 112; 520 mg, 1.6 mmol) and rac.-2-(dimethoxyphosphinyl)glycine methyl ester (Example 125) freshly prepared from rac.-N-(benzyloxycarbonyl)-2-(dimethoxyphosphinyl)glycine methyl ester (370 mg, 1.9 mmol). 1-hydroxybenzotriazole (255 mg, 1.9 mmol) was then added, followed by diisopropylethylamine (1.25 mL, 7.2 mmol). The solution was stirred at room temperature for 65 h and then it was evaporated to dryness under high vacuum to remove N,N-dimethylformamide. The residue was partitioned between ethyl acetate (50 mL) and saturated sodium bicarbonate solution (25 mL). The ethyl acetate layer was washed with brine, 0.5N hydrochloric acid solution and brine. Each of the aqueous layers was extracted with ethyl acetate. The combined organic extracts were dried (Na2SO4), filtered, evaporated and the residue was chromatographed over silica gel (50-100% ethyl acetate/hexanes, then 5-25% methanol/ethyl acetate) to give rac.-N-[2-chloro4-[[(3-hydroxybenzyl)amino]carbonyl]-6-methylbenzoyl]-2-(dimethoxyphosphinyl)glycine methyl ester (120 mg, 15% yield).

1. customit was evaporated to dryness under high vacuum
2. customto remove N,N-dimethylformamide
3. customThe residue was partitioned between ethyl acetate (50 mL) and saturated sodium bicarbonate solution (25 mL)
4. washThe ethyl acetate layer was washed with brine, 0.5N hydrochloric acid solution and brine
5. extractionEach of the aqueous layers was extracted with ethyl acetate
6. dry with materialThe combined organic extracts were dried (Na2SO4)
7. filtrationfiltered
8. customevaporated
9. customthe residue was chromatographed over silica gel (50-100% ethyl acetate/hexanes