Phosphate → (Z)-2-[[2-bromo-4-[[(3-hydroxybenzyl)amino]carbonyl]benzoyl]amino]-3-(quinolin-3-yl)propenoic acid methyl ester

Participants

Reaction Conditions

Reaction Steps

1,1,3,3-Tetramethylguanidine (0.5 mL, 4.0 mmol) was added to a solution of rac.-N-[2-bromo-4-[[(3-hydroxybenzyl)amino]carbonyl]benzoyl]-2-(dimethoxyphosphinyl)glycine methyl ester (Example 130; 1.00 g, 1.9 mmol) in tetrahydrofuran (8 mL) at −45° C. The solution was stirred at −45° C. for 5 min and then quinoline-3-carboxaldehyde (300 mg, 1.9 mmol) was added. After the reaction was allowed to proceed at −40° C. for 30 min, the mixture was warmed to room temperature and was stirred for another 2 h. Ethyl acetate and pH 6 phosphate buffer (200 mL each) were added and the resulting solid was filtered to furnish (Z)-2-[[2-bromo-4-[[(3-hydroxybenzyl)amino]carbonyl]benzoyl]amino]-3-(quinolin-3-yl)propenoic acid methyl ester (500 mg, 47% yield). The layers in the filtrate were separated and the aqueous phase was extracted with ethyl acetate (3×100 mL). The combined organic layers were dried (MgSO4), filtered through a bed of silica gel and the filtrate was evaporated to give an additional quantity of (Z)-2-[[2-bromo-4-[[(3-hydroxybenzyl)amino]carbonyl]benzoyl]amino]-3-(quinolin-3-yl)propenoic acid methyl ester (520 mg, 49% yield) as a colorless solid.

Provenance & Evidence