Methanol → N-{[4-((2R,3R)-1-(4-Fluorophenyl)-3-{[2-(4-fluorophenyl)-2-hydroxyethyl]thio}-4-oxoazetidin-2-yl)phenoxy]acetyl}glycyl-N,2-dimethylalanine

Participants

Reaction Conditions

Reaction Steps

To mixture of N-{[4-((2R,3R)-1-(4-fluorophenyl)-3-{[2-(4-fluorophenyl)-2-oxoethyl]thio}-4-oxoazetidin-2-yl)phenoxy]acetyl}glycine (0.020 g, 0.037 mmol) and NMM (0.012 ml, 0.109 mmol) in DMF (3 ml) at 30° C. was added TBTU (0.018 g, 0.056 mmol). The reaction mixture was stirred for 20 min after which 2-(methylamino)isobutyric acid (0.005 g, 0.038 mmol) was added. The mixture was stirred at 30° C. for 20 h before the reaction was quenched by the addition of water (1 ml). The mixture was diluted with MeOH (2 ml) and NaBH4(0.018 g, 0.486 mmol) was added. After 10 min the reaction was quenched by the addition of a 0.1M ammonium acetate buffer (2 ml) and most of the methanol was removed under reduced pressure. The remaining solution was purified by preparative HPLC using a gradient of 20-50% MeCN in a 0.1M ammonium acetate buffer as eluent. Freeze-drying of the pure fractions gave the desired product as a white solid (0.012 g, 50% yield).

Provenance & Evidence