1,1,3,3-Tetramethylguanidine → (Z)-2-[[2-chloro-4-[[(3-hydroxybenzyl)amino]carbonyl]-6-methylbenzoyl]amino]-3-[1-(1,1-dimethylethoxycarbonyl)-1H-benzotriazol-5-yl]propenoic acid methyl ester

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Reaction Steps

1,1,3,3-Tetramethylguanidine (60 μL, 0.48 mmol) was added to a solution of rac.-N-[2-chloro-4-[[(3-hydroxybenzyl)amino]carbonyl]-6-methylbenzoyl]-2-(dimethoxyphosphinyl)glycine methyl ester (Example 132; 109 mg, 0.22 mmol) in tetrahydrofuran (3 mL) at room temperature. 1-(1,1-dimethylethoxycarbonyl)-1H-benzotriazole-5-carboxaldehyde (Example 40; 55 mg, 0.22 mmol) was added and the solution was stirred at room temperature for 42 h. After the solvents were removed under reduced pressure, the residue was partitioned between ethyl acetate (10 mL) and pH 6 phosphate buffer (5 mL). The organic phase was washed with pH 6 phosphate buffer, brine, 10% aqueous sodium bicarbonate solution and brine. Each of the aqueous layers was extracted in turn with ethyl acetate. The combined organic layers were dried (Na2SO4), filtered and evaporated to give crude (Z)-2-[[2-chloro-4-[[(3-hydroxybenzyl)amino]carbonyl]-6-methylbenzoyl]amino]-3-[1-(1,1-dimethylethoxycarbonyl)-1H-benzotriazol-5-yl]propenoic acid methyl ester (120 mg) which was used directly in the next step.

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