4-Methylmorpholine → N-{[4-((2R,3R)-1-(4-fluorophenyl)-3-{[2-(4-fluorophenyl)-2-hydroxyethyl]thio)-4-oxoazetidin-2-yl)phenoxy]acetyl}glycyl-3-methyl-D-isovaline

Participants

Reaction Steps

N-{[4-((2R,3R)-1-(4-Fluorophenyl)-3-{[2-(4-fluorophenyl)-2-oxoethyl]thio}-4-oxoazetidin-2-yl)phenoxy]acetyl}glycine (0.035 g, 0.065 mmol) was dissolved in DMF (2 ml) at 30° C. N-Methyl morpholine (0.026 g, 0.259 mmol) and TBTU (0.027 g, 0.084 mmol) were added. After 1 h, 3-methyl-D-isovaline (0.013 g, 0.097 mmol) was added. The mixture was stirred for 2 h and water (1 ml) was added. After 10 minutes, MeOH (2 ml) and NaBH4 (0.037 g, 0.971 mmol) were added. Full conversion to the corresponding alcohol was obtained after 5 minutes and 0.1M NH4OAc buffer (2 ml) was added. The mixture was purified by preparative HPLC (eluent 0-50% CH3CN in 0.1M NH4OAc buffer). Freeze-drying of the pure fractions afforded the title compound (0.020 g, 47%) as a colourless solid. M/z: 654.0 (M−1). 1H NMR [(CD3)2SO), 400 MHz] δ 0.79 (d, 3H), 0.87 (d, 3H), 1.29 (s, 3H), 2.00-2.07 (m, 1H), 2.84-2.94 (m, 2H), 3.73 (d, 2H), 4.25-4.28 (m, 1H), 4.51 (s, 2H), 4.69-4.75 (m, 1H), 5.03-5.06 (m, 1H), 6.97-7.37 (m, 12H), 7.82 (s, 1H), 8.24 (t, 1H).

Provenance & Evidence