Potassium Carbonate → HCID 69363757, compound

Temperature

100 °C

Under a nitrogen atmosphere, 4-(methylthio) phenol (4.2 g) and bromoethanol (5.6 g) were dissolved in dimethylformamide solution (60 ml), potassium carbonate (12.4 g) was added, and the mixture was heating under stirring at 100° C. After 3 hours, the mixture was cooled to room temperature, then the organic layer was separated by adding diethyl ether and water thereto. The resulting organic layer was washed with water and brine, and dried over anhydrous magnesium sulfate. After filtering off the drying agent, the mixture was evaporated. The residue was purified by silica gel column chromatography (hexane/ethyl acetate system), to give (4-methylthiophenoxy) ethanol (3.55 g, 64%) as white crystals. The product (1.0 g) was dissolved in dichloromethane (50 ml), the mixture was cooled on a methanol-dry ice bath, methachloroperbenzoic acid (3.6 g) was added, and the mixture was stirred. After cooling naturally to room temperature over 2 hours, a 1N aqueous sodium bicarbonate and 1N Na2S2O3 were added. After stirring, the mixture was extracted with dichloromethane, and dried over anhydrous magnesium sulfate. After filtering off the drying agent, the mixture was evaporated. The residue was dissolved in acetonitrile (18 ml), triethylamine (2.3 ml) and methanesulfonyl chloride (0.5 ml) were added, and the mixture was stirred at room temperature. After 1.5 hours, sodium iodide (4.9 g) and tert-butyl-1-piperazinecarboxylate (1.2 g) were added, and the mixture was heated under stirring at 60° C. After stirring for 4.5 hours, the organic layer was separated by adding ethyl acetate and water. The resulting organic layer was washed with water and brine, and dried over anhydrous magnesium sulfate. After filtering the drying agent, the mixture was evaporated. The residue was purified by silica gel column chromatography (hexane/ethyl acetate system), to give tert-butyl-2-(4-methylthiophenoxy)ethyl-1-piperazinecarboxylate (1.15 g) as white crystals. The product (1.15 g) was dissolved in methanol (10 ml), and the solution was added to a 4N hydrochloric acid-ethyl acetate solution (30 ml) in an ice bath. After stirring at room temperature overnight, the resulting white crystals were collected by filtration and washed with diethyl ether. A 1N aqueous sodium hydroxide and dichloromethane were added to the crystals, to separate the organic layer. The resulting organic layer was evaporated, to give the title compound as a yellow oil (820 mg, 53%; 3 steps).

1. temperaturethe mixture was heating
2. temperaturethe mixture was cooled to room temperature
3. customthe organic layer was separated
4. additionby adding diethyl ether and water
5. washThe resulting organic layer was washed with water and brine
6. dry with materialdried over anhydrous magnesium sulfate
7. filtrationAfter filtering off the drying agent
8. customthe mixture was evaporated
9. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate system)

ORD record

ord-f304fabf26d948d787582eae69b4bc93

Source dataset

uspto-grants-2005_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06906072B1