反应详情

To a solution of (3R)-3-methylmorpholine (88 mg, 0.872 mmol, Tyger Scientific, Ewing, USA) in methanol (2 mL) was added formaldehyde (37% aqueous) (0.065 mL, 0.872 mmol). The reaction mixture was stirred at room temperature for 2 hours before the addition of 2-isocyano-5-(trifluoromethyl)pyridine (150 mg, 0.872 mmol, commercially available from Priaxon AG, Munich, Germany) and trimethylsilylazide (0.116 mL, 0.872 mmol). The reaction mixture was stirred at room temperature overnight (approximately 18 hours) and the solvent removed under vacuum. The residue was purified by MDAP. Fractions containing the desired compound were combined and the solvent removed. The residue was partitioned between saturated NaHCO3 (2 mL) and DCM (5 ml). The organic layer was collected via a hydrophobic frit and the solvent removed under a stream of argon to yield a colourless gum. The compound was dissolved in a minimum of diethyl ether and methanol before the addition of 1N HCl in diethyl ether (2 mL) The solvent was removed under a stream of argon and the residue dried under vacuum at 40° C. for 18 hours to yield a white solid. The compound was triturated with diethyl ether (0.5 mL) and the solvent decanted. The solid was dried under vacuum at 40° C. for 18 hours to yield the title compound as a white solid (11 mg)

1. customthe solvent removed under vacuum
2. customThe residue was purified by MDAP
3. additionFractions containing the desired compound
4. customthe solvent removed
5. customThe residue was partitioned between saturated NaHCO3 (2 mL) and DCM (5 ml)
6. customThe organic layer was collected via a hydrophobic frit
7. customthe solvent removed under a stream of argon
8. customto yield a colourless gum
9. customwas removed under a stream of argon
10. customthe residue dried under vacuum at 40° C. for 18 hours
11. customto yield a white solid
12. customThe compound was triturated with diethyl ether (0.5 mL)
13. customthe solvent decanted
14. customThe solid was dried under vacuum at 40° C. for 18 hours