反应详情

Methyl-3-bromomethylbenzoate (5.72 g, 0.025 mol, Ryan Chemicals (Maybridge)), sodium azide (3.25 g, 0.05 mol), and tetra n-butylbromide (0.4 g, 0.00125 mol) were added to 100 mL dry benzene in a 250-mL round-bottom flask equipped with a condenser and calcium chloride drying tube in an atmosphere of argon. The mixture was then heated at reflux for 24 h and monitored by TLC (Bakerflex) using dichloromethane, 2% methanol, and 5% methanol/dichloromethane as solvents. The mixture was cooled, the inorganic salts were removed by filtration, and washed with benzene. The filtrate was added to a 250-mL separatory funnel and was then washed three times with water, once with brine, and dried with magnesium sulfate. The drying agent was removed by filtration, and the volume of the clear colorless filtrate was reduced to ~50 mL in a 100-mL round-bottom flask. The solution was saturated with argon and 3.1 g (0.025 mol) trimethylphosphite was added by drop over 10 min. The reaction bubbled during the addition (loss of nitrogen) and was mildly exothermic (once it was necessary to cool on ice with a calcium chloride drying tube in place to keep the temperature below 30° C.). The reaction was followed in the TLC system above and after 18 h, it was necessary to add ~200 mg of additional trimethylphosphite. The reaction was complete after stirring overnight. Anhydrous HCl was then bubbled into the solution with vigorous stirring. After 2 h, a precipitate formed and alter 4 h, the reaction was complete. The white solid was removed by filtration. It was then added to 200 mL ether in a 500-mL Erlenmeyer flask and vigorously stirred for 5 min. After filtration, the solid was dissolved in a minimum amount of boiling methanol and ether was added until the solution was slightly turbid. Cooling, filtering, and drying in vacuo gave 4.2 g (83%) of methyl-3-aminomethylbenzoate hydrochloride, mp 177°-178° C.

1. customequipped with a condenser and calcium chloride drying tube in an atmosphere of argon
2. temperatureThe mixture was then heated
3. temperatureat reflux for 24 h
4. temperatureThe mixture was cooled
5. customthe inorganic salts were removed by filtration
6. washwashed with benzene
7. additionThe filtrate was added to a 250-mL separatory funnel
8. washwas then washed three times with water
9. dry with materialonce with brine, and dried with magnesium sulfate
10. customThe drying agent was removed by filtration
11. customthe volume of the clear colorless filtrate was reduced to ~50 mL in a 100-mL round-bottom flask
12. additionwas added by drop over 10 min
13. customThe reaction bubbled during the addition (loss of nitrogen)
14. temperatureto cool on ice with a calcium chloride drying tube in place
15. customthe temperature below 30° C.
16. customafter 18 h
17. additionto add ~200 mg of additional trimethylphosphite
18. customAnhydrous HCl was then bubbled into the solution with vigorous stirring
19. waitAfter 2 h
20. customa precipitate formed
21. waitalter 4 h
22. customThe white solid was removed by filtration
23. additionIt was then added to 200 mL ether in a 500-mL Erlenmeyer flask
24. stirringvigorously stirred for 5 min
25. filtrationAfter filtration
26. dissolutionthe solid was dissolved in a minimum amount of boiling methanol and ether
27. additionwas added until the solution
28. temperatureCooling
29. filtrationfiltering
30. customdrying in vacuo