4-Methylmorpholine → HCID 66843103, compound

Participants

Reaction Steps

N-{[4-((2R,3R)-1-(4-fluorophenyl)-3-{[2-(4-fluorophenyl)-2-oxoethyl]thio}-4-oxoazetidin-2-yl)phenoxy]acetyl}glycine (0.025 g, 0.046 mmol) was dissolved in DMF (2 ml) at 30° C. N-Methyl morpholine (0.034 g, 0.333 mmol) and TBTU (0.043 g, 0.133 mmol) were added. After 1 h, sodium (2R)-2-amino-4-cyclohexylbutanoate (0.039 g, 0.189 mmol), DMSO (2 ml) and tetrabutylammoniumbromide (0.004 g, 0.011 mmol) were added. The mixture was stirred for 1 h and water (1 ml) was added. After 1 h, MeOH (2 ml) and NaBH4 (0.084 g, 2.220 mmol) were added. Full conversion to the corresponding alcohol was obtained after 5 minutes. The reaction was quenched by the addition of 0.1M NH4OAc buffer (2 ml). The mixture was purified by preparative HPLC (eluent 0-50% CH3CN in 0.1M NH4OAc buffer). Freeze-drying of the pure fractions gave the title compound (0.034 g, 43%) as a colourless solid. M/z: 708.1 (M−1). 1H NMR [(CD3)2SO), 400 MHz] δ 0.75-1.62 (m, 15H), 2.82-2.99 (m, 2H), 3.68-3.78 (m, 2H), 3.90-3.96 (m, 1H), 4.23-4.35 (m, 1H), 4.50 (s, 2H), 4.69-4.75 (m, 1H), 5.01-5.07 (m, 1H), 6.95-7.39 (m, 12H), 7.68-7.80 (m, 1H), 8.20-8.34 (m, 1H).

Provenance & Evidence