50-00-0

24424-99-5

542-92-7

188345-71-3

Example 3A Synthesis of tert-butyl 2-azabicyclo[2.2.1]hept-5-ene-2-carboxylate: 37% aqueous formaldehyde (114 mL, 1.41 mol) was slowly added to a vigorously stirred aqueous NH4Cl solution (85.0 g, 1.59 mol, 250 mL water). Subsequently, freshly distilled cyclopentadiene (170 g, 2.58 mol) was added all at once and the reaction mixture was stirred continuously for 17 hours at room temperature. Upon completion of the reaction, the lower aqueous phase was separated and treated with di-tert-butyl dicarbonate (172 g, 0.78 mol). The pH of the reaction system was adjusted to about 8 by dropwise addition of 1 M NaOH aqueous solution (100 mL) and stirring was continued at room temperature for 7 h, during which time solid NaOH (40 g in total) was added in batches to maintain the pH at about 8. The reaction mixture was extracted with hexane (2 x 200 mL) and the combined organic phases were washed with brine (50 mL), dried over anhydrous MgSO4 and concentrated under reduced pressure. The residue was purified by subtractive distillation and the fractions with boiling points of 80-92 °C/10 mmHg were collected to afford tert-butyl 2-azabicyclo[2.2.1]-5-heptene-2-carboxylate (123 g, 0.63 mol, 45% yield) as a light yellow liquid, which was crystallized after cooling. The product was characterized by 1H NMR (CDCl3, 300 MHz) and MS (DCI/NH3) and the data were consistent with the expected structure.