Sodium Iodide → 2-(3-(cyclopropylmethoxy)phenyl)-N-methylethanamine

Temperatur

80 °C

3-(2-Hydroxyethyl)phenol (2.5 g) was dissolved in DMF (18 mL). To the solution, potassium carbonate (5.0 g), sodium iodide (271 mg), and (chloromethyl)cyclopropane (1.75 mL) were added, and the mixture was stirred at 80° C. for 5 hours. The reaction mixture was cooled to room temperature, water (40 mL) was then added thereto, and the resultant mixture was then extracted with ethyl acetate (40 mL). The organic layer was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (17% ethyl acetate/hexane). An aliquot (500 mg) of the obtained monoalcohol compound (2.6 g) was dissolved in dichloromethane (10 mL). To the solution, triethylamine (540 μL) and methanesulfonyl chloride (242 μL) were added, and the mixture was stirred at room temperature for 30 minutes. To the reaction mixture, an aqueous saturated sodium bicarbonate solution (10 mL) was added, and the resultant mixture was partitioned. The organic layer was washed with water (10 mL) and brine (10 mL), dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The residue was dissolved in THF (6.0 mL). To the solution, an aqueous methylamine solution (40%, 6.0 mL) was added, and the mixture was stirred at 60° C. for 4 hours in a sealed tube. The reaction mixture was cooled to room temperature and then concentrated under reduced pressure. To the residue, an aqueous sodium hydroxide solution (1.0 M, 10 mL) was added, and the resultant mixture was then extracted with diethyl ether (20 mL). The organic layer was extracted with dilute hydrochloric acid (1.0 M, 20 mL), and the aqueous layer was turned into basic by the addition of an aqueous sodium hydroxide solution (4.0 M, 20 mL), and was then extracted with diethyl ether (20 mL). The organic layer was dried over potassium carbonate and concentrated under reduced pressure to obtain the title compound (310 mg) as a colorless oil.

1. temperatureThe reaction mixture was cooled to room temperature
2. extractionthe resultant mixture was then extracted with ethyl acetate (40 mL)
3. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
4. concentrationconcentrated under reduced pressure
5. customThe residue was purified by silica gel column chromatography (17% ethyl acetate/hexane)
6. dissolutionAn aliquot (500 mg) of the obtained monoalcohol compound (2.6 g) was dissolved in dichloromethane (10 mL)
7. additionTo the solution, triethylamine (540 μL) and methanesulfonyl chloride (242 μL) were added
8. stirringthe mixture was stirred at room temperature for 30 minutes
9. additionTo the reaction mixture, an aqueous saturated sodium bicarbonate solution (10 mL) was added
10. customthe resultant mixture was partitioned
11. washThe organic layer was washed with water (10 mL) and brine (10 mL)
12. dry with materialdried over anhydrous magnesium sulfate
13. concentrationconcentrated under reduced pressure
14. dissolutionThe residue was dissolved in THF (6.0 mL)
15. additionTo the solution, an aqueous methylamine solution (40%, 6.0 mL) was added
16. stirringthe mixture was stirred at 60° C. for 4 hours in a sealed tube
17. temperatureThe reaction mixture was cooled to room temperature
18. concentrationconcentrated under reduced pressure
19. additionTo the residue, an aqueous sodium hydroxide solution (1.0 M, 10 mL) was added
20. extractionthe resultant mixture was then extracted with diethyl ether (20 mL)
21. extractionThe organic layer was extracted with dilute hydrochloric acid (1.0 M, 20 mL)
22. additionbasic by the addition of an aqueous sodium hydroxide solution (4.0 M, 20 mL)
23. extractionwas then extracted with diethyl ether (20 mL)
24. dry with materialThe organic layer was dried over potassium carbonate
25. concentrationconcentrated under reduced pressure

ORD-Eintrag

ord-f5ff07c9d6b64c92968e6804800d9212

Quelldatensatz

uspto-grants-2013_09

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08530490B2