反应详情

温度

-40 °C

1,1,3,3-Tetramethylguanidine (50 μL, 0.397 mmol) was added to a solution of rac.-N-[2-bromo-4-[[(3-hydroxybenzyl)amino]carbonyl]benzoyl]-2-(dimethoxyphosphinyl)glycine methyl ester (Example 130; 100 mg, 0.189 mmol) in tetrahydrofuran (2 mL) at −40° C. The solution was stirred at −40° C. for 5 min and then 2-methylthiazole-4-carboxaldehyde (Example 41; 48 mg, 0.378 mmol) was added. The solution was stirred at −40° C. for 1 h and then allowed to stir at room temperature for 4 h. The solution was quenched with pH 6 phosphate buffer, diluted with ethyl acetate (15 mL) and the separated organic layer was washed with pH 6 phosphate buffer (10 mL) and brine (10 mL). The organic phase was dried (MgSO4), filtered, evaporated and triturated with diethyl ether to give (Z)-2-[[2-bromo-4-[[(3-hydroxybenzyl)amino]carbonyl]benzoyl]amino]-3-(2-methylthiazol-4-yl)propenoic acid methyl ester (92 mg, 49% yield) as a brown solid.

1. stirringThe solution was stirred at −40° C. for 1 h
2. stirringto stir at room temperature for 4 h
3. customThe solution was quenched with pH 6 phosphate buffer
4. additiondiluted with ethyl acetate (15 mL)
5. washthe separated organic layer was washed with pH 6 phosphate buffer (10 mL) and brine (10 mL)
6. dry with materialThe organic phase was dried (MgSO4)
7. filtrationfiltered
8. customevaporated
9. customtriturated with diethyl ether