Morpholine → 4-(Morpholinomethyl)thiazole

4-Methylthiazole (1.98 g), N-bromosuccinimide (3.56 g) and α,α′-azobisisobutyronitrile (164 mg) were dissolved in carbon tetrachloride (200 ml), and the solution was heated under reflux for 2 hours. After completion of the reaction, insoluble matter was removed by filtration, N,N-dimethylformamide (20 ml) was added to the filtrate, and carbon tetrachloride was distilled off under reduced pressure to obtain an N,N-dimethylformamide solution (about 20 ml) of 4-(bromomethyl)thiazole. Morpholine (871 μl), triethylamine (2.79 ml) and N,N-dimethylformamide (10 ml) were successively added to this N,N-dimethyl-formamide solution (about 10 ml) of 4-(bromomethyl)-thiazole, and the mixture was stirred overnight at room temperature. The solvent was distilled off under reduced pressure, dichloromethane and a saturated aqueous solution of sodium hydrogen carbonate were added to the residue and an organic layer was separated. The organic layer was dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the residue was purified by column chromatography on silica gel (methanol:dichloromethane=1:19) to obtain the title compound (700 mg) as a yellow oil.

1. distillationThe solvent was distilled off under reduced pressure, dichloromethane
2. additiona saturated aqueous solution of sodium hydrogen carbonate were added to the residue
3. customan organic layer was separated
4. dry with materialThe organic layer was dried over anhydrous sodium sulfate
5. distillationThe solvent was distilled off under reduced pressure
6. customthe residue was purified by column chromatography on silica gel (methanol:dichloromethane=1:19)

ORD record

ord-c3446e35cfc74dd1b31851b1d2e3efda

Source dataset

uspto-grants-2011_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07935824B2