Benzene → Methyl 4-[(methylamino)carbonyl]benzoate

Monomethylterephthalate (Aldrich, 5.0 g, 0.028 mol) was added to 80 mL of dry benzene in a 250-mL round-bottom flask under argon and fitted with a calcium chloride drying tube. Dry pyridine (4.4 g, 0.056 mol) was added and the mixture was stirred for 15 min. Oxalyl chloride (3.66 g, 0.029 mol) was added by drop over 10 min. The mixture bubbled vigorously during the addition and a heavy white precipitate formed. The mixture was vigorously stirred for 40 min and followed by TLC (three solvent systems: dichloromethane, 2% methanol, and 5% methanol). Anhydrous methylamine was bubbled into the mixture for 10 min. The precipitate dissipated somewhat and the solution color changed from colorless to green and finally to yellow. The mixture was then stirred overnight. The remaining white precipitate was collected on a filter and washed with benzene. The filtrate was washed with water and dried over sodium sulfate. The drying agent was removed by filtration, washed with benzene, and the solvent concentrated to give a white solid. The solids were combined and dissolved in 300 mL dichloromethane. The solution was washed 3 times with 5% HCl, 3×5% sodium bicarbonate, 3×water, 1×brine, and then dried over sodium sulfate. The drying agent was removed by filtration and the filtrate concentrated to give a white solid which was dried in vacuo. This white solid was recrystallized from methanol to give 2 g (37%) of methyl 4-(methylaminocarbonyl)benzoate, mp 126° C.

1. customfitted with a calcium chloride drying tube
2. customThe mixture bubbled vigorously during the addition
3. customa heavy white precipitate formed
4. stirringThe mixture was vigorously stirred for 40 min
5. customAnhydrous methylamine was bubbled into the mixture for 10 min
6. stirringThe mixture was then stirred overnight
7. customThe remaining white precipitate was collected on
8. filtrationa filter
9. washwashed with benzene
10. washThe filtrate was washed with water
11. dry with materialdried over sodium sulfate
12. customThe drying agent was removed by filtration
13. washwashed with benzene
14. concentrationthe solvent concentrated
15. customto give a white solid
16. washThe solution was washed 3 times with 5% HCl, 3×5% sodium bicarbonate, 3×water, 1×brine
17. dry with materialdried over sodium sulfate
18. customThe drying agent was removed by filtration
19. concentrationthe filtrate concentrated
20. customto give a white solid which
21. customwas dried in vacuo
22. customThis white solid was recrystallized from methanol

ORD record

ord-0ad867a7c4d243f7acf6d4913f5ab244

Source dataset

uspto-grants-1997_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05602277