Water → ((tetrahydro-2H-pyran-2-yl)methyl)hydrazine dihydrochloride

Temperatur

50 °C

A solution of the Compound (Ih) (10 g, 58 mmol), 2-(tetrahydropyranyl)methylbromide (10 mL, 81 mmol), potassium hydroxide (4.89 g, 87 mmol) and tetrabutyl-ammonium sulfate (1.97 g, 5.8 mmol) in toluene (200 mL) was heated under reflux for 9 hours. To the reaction mixture was added water (200 mL), and the aqueous layer was extracted with ethyl acetate (200 mL). The combined organic layers were dried over anhydrous MgSO4 and the solvent was evaporated under reduced pressure. The concentrated residue was purified by silica gel column chromatography (n-hexane/ethyl acetate) to give Compound (IIh) (9.30 g). The Compound (IIh) was dissolved in a mixed solvent of methanol (65 mL) and chloroform (30 mL), to the solution was added 4 mol/L HCl/1,4-dioxane (65 mL) at room temperature, and the reaction mixture was stirred at 50° C. for 1 hour. The solvent was evaporated under reduced pressure, to the concentrated residue was added ethyl acetate (100 mL), and the mixture was stirred for 1 hour at room temperature. The resulting precipitate was collected by filtration, washed with ethyl acetate (5 mL) twice, and dried under reduced pressure to give the title Compound (IIIh) (6.79 g, 70%) as a white solid.

1. temperatureunder reflux for 9 hours
2. extractionthe aqueous layer was extracted with ethyl acetate (200 mL)
3. dry with materialThe combined organic layers were dried over anhydrous MgSO4
4. customthe solvent was evaporated under reduced pressure
5. customThe concentrated residue was purified by silica gel column chromatography (n-hexane/ethyl acetate)
6. customto give Compound (IIh) (9.30 g)
7. customThe solvent was evaporated under reduced pressure, to the concentrated residue
8. additionwas added ethyl acetate (100 mL)
9. stirringthe mixture was stirred for 1 hour at room temperature
10. filtrationThe resulting precipitate was collected by filtration
11. washwashed with ethyl acetate (5 mL) twice
12. customdried under reduced pressure

ORD-Eintrag

ord-4f4c5cbe547145bb9a2ac8da8b72e346

Quelldatensatz

uspto-grants-2013_10

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08569353B2