Compound TDG4

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Synthetic procedure: See article for the definitive version of this procedure and for full experimental details.

To a stirring solution of Boc-L-Tle-OH (5 mmol), EDC-HCl (1.05 g, 5.5 mmol), HOAt (748.6 mg, 5.5 mmol) and HNEt₂-HCl (602.8 mg, 5.5 mmol) in DCM (15 mL), was added N,N-Diisopropylethylamine (1.05 mL, 6 mmol) dropwise at 0 ^oC. The reaction mixture was slowly warmed to room temperature, and stirred for 24 h. Upon completion, the reaction mixture was diluted with DCM, washed with 10 % KHSO₄ (aq), sat. NaHCO₃ (aq), and brine. The organic layer was dried over anhydrous MgSO₄, filtered and concentrated in vacuo. The crude residue was purified by flash chromatography to afford Boc-L- Tle-NEt₂. The product was dissolved in DCM (5 mL), TFA (5 mL) was added dropwise, and the resulting solution was stirred at room temperature. Upon completion, solvent was removed in vacuo, and diethyl ether was added to precipitate the TFA salt of TDG4. The collected TFA salt was dissolved in sat. Na₂CO₃ (aq), and extracted with DCM. The combined organic layers were dried over anhydrous Na₂SO₄, filtered and concentrated in vacuo to afford TDG4 as a clear oil. The spectroscopic data was consistent with reported values (Martin, N. J. A., Cheng, X. & List, B. Organocatalytic Asymmetric Transferhydrogenation of β-Nitroacrylates: Accessing β²-Amino Acids. J. Am. Chem. Soc. 130, 13862-13863 (2008)). The racemic transient DG was prepared from racemic starting material.