1,1,3,3-Tetramethylguanidine → (Z)-2-[[4-[[[3-[[(1,1-dimethylethyl)dimethylsilyl]oxy]benzyl]amino]carbonyl]-2,6-dimethylbenzoyl]amino]-3-(2,4-dimethylthiazol-5-yl)propenoic acid methyl ester

Participants

Reaction Conditions

Reaction Steps

1,1,3,3-Tetramethylguanidine (54 μL, 0.425 mmol) was added to a solution of rac.-2-(dimethoxyphosphinyl)-N-[4-[[[3-[[(1,1-dimethylethyl)dimethylsilyl]oxy]benzyl]amino]carbonyl]-2,6-dimethylbenzoyl]glycine methyl ester (Example 126; 150 mg, 0.25 mmol) in tetrahydrofiran (2 mL) at −40° C. The solution was stirred at −40° C. for 5 min and then 2,4-dimethylthiazol-5-carboxaldehyde (Example 43; 43 mg, 0.3 mmol) was added. The reaction mixture was stirred at −40° C. for 60 min and then allowed to stir at room temperature for 4 h. A second portion of 1,1,3,3-tetramethylguanidine (27 μL, 0.213 mmol) and the reaction was allowed to stir at room temperature for 2 days. The solution was partitioned between pH 6 phosphate buffer and ethyl acetate and the organic layer was dried (MgSO4), filtered and evaporated. The residue was chromatographed (silica gel, ethyl acetate in petroleum ether) to furnish 78 mg of (Z)-2-[[4-[[[3-[[(1,1-dimethylethyl)dimethylsilyl]oxy]benzyl]amino]carbonyl]-2,6-dimethylbenzoyl]amino]-3-(2,4-dimethylthiazol-5-yl)propenoic acid methyl ester as a colorless foam (50% yield).

Provenance & Evidence