Dimethylformamide → HCID 69363635, compound

Temperature

100 °C

Under a nitrogen atmosphere, 3-hydroxyacetophenone (4.1 g) and brominated ethanol (5.6 g) were dissolved in dimethylformamide solution (60 ml), and potassium carbonate (12.4 g) was added, and the mixture was heated under stirring at 100° C. After 3 hours, the mixture was cooled to room temperature, and the organic layer was separated by adding water and diethyl ether 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 (3-acetylphenoxy) ethanol (3.28 g, 61%) as white crystals. The product (977 mg) 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 water and ethyl acetate 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 tert-butyl-2-(3-acetylphenoxy)ethyl-1-piperazinecarboxylate (1.33 g) as a yellow oil. The product (1.33 g) was dissolved in methanol (10 ml), and the solution was added to a 4N hydrochloric acid-ethyl acetate solution (30 ml). The mixture was stirred at a room temperature overnight, the resulting white crystals were collected by filtration and washed with diethyl ether. The organic layer was separated by adding a 1N aqueous sodium hydroxide and dichloromethane to the crystals. The resulting organic layer was evaporated, to give the title compound (830 mg, 62%; 2 steps) as a yellow oil.

1. temperaturethe mixture was heated
2. temperaturethe mixture was cooled to room temperature
3. customthe organic layer was separated
4. additionby adding water and diethyl ether
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-72e1f14a80374e1cbb26501d7b2ea144

Source dataset

uspto-grants-2005_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06906072B1