4-Methylmorpholine → HCID 178462345, compound

Participants

Reaction Conditions

Reaction Steps

N-Boc-L-allo-threonine (Preparation 54, 67.12 g, 306 mmol), 4-tert-butyl-diaminobenzene (60.3 g, 367 mmol) and HOBt (56.3 g, 367 mmol) were dissolved in DMF (500 mL). NMM (67 mL, 612 mmol) was added and the mixture cooled to 0° C. EDCI (65.6 g, 336 mmol) was added portionwise over 1.5 hours and the reaction was stirred at room temperature for 18 hours. EtOAc (2 L) was added followed by water (10 and the mixture stirred vigorously for 15 minutes. The aqueous layer was removed and washed further with EtOAc (2×30 mL). The organic layers were combined, dried over Na2SO4 and concentrated in vacuo. The residue was sonicated in pentane/DCM 10/1 twice and filtered to afford a pale pink solid that was dissolved in AcOH (500 mL) and stirred at 40° C. for 24 hours followed by room temperature for 2 days. The solvent was removed in vacuo and the residue dissolved in EtOAc (1.5 L). Saturated aqueous NaHCO3 (500 mL) was added and the mixture stirred vigorously. The organic layer was collected, washed with NaHCO3 solution (2×200 mL), dried over Na2SO4 and concentrated in vacuo. The residue was dissolved in DCM (500 mL) and purified using silica gel column chromatography eluting with 0-20% acetone in cyclohexaneto afford the title compound as an off-white solid (89 g, quant).

Provenance & Evidence