1,1,3,3-Tetramethylguanidine → (Z)-2-[[2-chloro-4-[[(3-hydroxybenzyl)amino]carbonyl]benzoyl]amino]-3-[4-(1-methylethyl)thiazol-5-yl]propenoic acid methyl ester

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Reaction Steps

1,1,3,3-Tetramethylguanidine (41 μL, 0.33 mmol) was added to a solution of rac.-N-[2-chloro-4-[[(3-hydroxybenzyl)amino]carbonyl]benzoyl]-2-(dimethoxyphosphinyl)glycine methyl ester (Example 141; 75 mg, 0.15 mmol) in tetrahydrofuran (2 mL) at about −25° C. After 5 min, a solution of 4-(1-methylethyl)thiazole-5-carboxaldehyde (Example 56; 26 mg, 0.168 mmol) in tetrahydrofuran (1 mL) was added. The cooling bath was removed and the solution was stirred at room temperature for 17 h. The solvent was evaporated and the residue was partitioned between ethyl acetate (10 mL) and 10% aqueous acetic acid (5 mL). The ethyl acetate layer was washed with brine and each of the aqueous layers was extracted with ethyl acetate (10 mL). The combined organic extracts were dried (Na2SO4), filtered and evaporated to give a colorless foam which was triturated with diethyl ether (5 mL). The resulting solids were recovered by filtration to furnish (Z)-2-[[2-chloro-4-[[(3-hydroxybenzyl)amino]carbonyl]benzoyl]amino]-3-[4-(1-methylethyl)thiazol-5-yl]propenoic acid methyl ester (76 mg, 99% yield).

Provenance & Evidence