1,1,3,3-Tetramethylguanidine → Rac.-(z)-2-[[2-chloro-4-[1-hydroxy-3-(3-hydroxyphenyl)propan-1-yl]benzoyl]amino]-3-(2,4-dimethylthiazol-5-yl)propenoic acid methyl ester

Participants

Reaction Steps

1,1,3,3-Tetramethylguanidine (60 μL, 0.48 mmol) was added to a solution of rac.-N-[2-chloro-4-[1-hydroxy-3-(3-hydroxyphenyl)propan-1-yl]benzoyl]-2-(dimethoxyphosphinyl)glycine methyl ester (Example 134; 120 mg, 0.24 mmol) in tetrahydrofuran (5 mL) at −20° C. After 10 min, 2,4-dimethylthiazole-5-carboxaldehyde (Example 43; 36 mg, 0.255 mmol) was added and the solution was stirred at room temperature for 16 h. After the volatiles were removed in vacuo, ethyl acetate (10 mL) was added. The resulting solution was washed with saturated sodium bicarbonate solution (5 μL) and the aqueous layer was extracted with ethyl acetate. The combined organic layers were dried (MgSO4), filtered, evaporated and chromatographed over silica gel (3:2 ethyl acetate/hexanes). The appropriate fractions were combined, evaporated and the residue triturated with diethyl ether to yield rac.-(Z)-2-[[2-chloro-4-[1-hydroxy-3-(3-hydroxyphenyl)propan-1-yl]benzoyl]amino]-3-(2,4-dimethylthiazol-5-yl)propenoic acid methyl ester (88 mg, 75% yield) as a colorless solid.

Provenance & Evidence