1,1,3,3-Tetramethylguanidine → (Z)-2-[[2-chloro-4-[3-(3-hydroxyphenyl)-1-oxopropan-1-yl]benzoyl]amino]-3-(2,4-dimethylthiazol-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-(3-hydroxyphenyl)-1-oxopropan-1-yl]benzoyl]-2-(dimethoxyphosphinyl)glycine methyl ester (Example 133; 116 mg, 0.24 mmol) in tetrahydrofuran (6 mL) at −20° C. After 15 min, 2,4-dimethylthiazole-5-carboxaldehyde (Example 43; 37 mg, 0.26 mmol) was added and the solution was stirred at room temperature for 16 h. The solvent was evaporated and ethyl acetate (15 mL) was added. The resulting solution was washed with saturated sodium bicarbonate solution (15 mL) and brine. The organic layer was dried (MgSO4), filtered, evaporated, chromatographed over silica gel (60% ethyl acetate/hexanes) and crystallized from diethyl ether/hexanes to (Z)-2-[[2-chloro-4-[3-(3-hydroxyphenyl)-1-oxopropan-1-yl]benzoyl]amino]-3-(2,4-dimethylthiazol-5-yl)propenoic acid methyl ester (98 mg, 82% yield) as a colorless solid.

Provenance & Evidence