Boc-Thr-OBzl

Uses

Boc-Thr-Obzl is used in preparation of of substituted Oxopyridine derivatives as factor XIa and plasma kallikrein inhibitors useful in treating Thrombotic or Thromboembolic diseases.

Synthesis

The general procedure for the synthesis of the target compound (CAS: 140422-54-4) from (2S,3R)-2-((tert-butoxycarbonyl)amino)-3-hydroxybutanoic acid (Boc-L-threonine, 1.32 g, 6.03 mmol) and benzyl bromide (783 μL, 1.13 g, 6.63 mmol) was as follows: dissolve Boc-L-threonine in methanol (40 mL) and cesium carbonate (Cs2CO3, 1.08 g, 3.32 mmol) was added. After complete dissolution, the solution was concentrated. Subsequently, the concentrate was dissolved in N,N-dimethylformamide (DMF, 20 mL) and benzyl bromide was added. The reaction mixture was stirred at room temperature for 18 hours. After completion of the reaction, the solvent was removed by evaporation. The crude product was dissolved in water (20 mL) and extracted with dichloromethane (3 × 20 mL). The organic phase was dried over anhydrous magnesium sulfate (MgSO4) and the solvent was evaporated to give the crude product. The target compound (1.73 g, 5.58 mmol, 93% yield) was purified by silica gel fast column chromatography (eluent: hexane/ethyl acetate, 5:1). Thin layer chromatography (TLC) showed Rf = 0.16 (Expanding agent: hexane/ethyl acetate, 5:1, potassium permanganate solution showed color). Nuclear magnetic resonance hydrogen (1H-NMR, 500 MHz, CDCl3) and carbon (13C-NMR, 125 MHz, CDCl3) spectral data were consistent with the structure of the target compound. Mass spectrometry (MS) and high performance liquid chromatography-mass spectrometry (HRMS) data further confirmed the molecular weight and structure of the target compounds.

References

[1] Journal of the American Chemical Society, 2014, vol. 136, # 18, p. 6754 - 6762
[2] Tetrahedron, 2012, vol. 68, # 2, p. 697 - 704
[3] Organic letters, 2002, vol. 4, # 8, p. 1335 - 1338
[4] Organic Letters, 2010, vol. 12, # 22, p. 5306 - 5309
[5] Chemistry - A European Journal, 2016, vol. 22, # 47, p. 16912 - 16919