反应详情

温度

90 °C

A solution of a mixture of 1-azabicyclo[2.2.2]oct-3-yl(2-bromo-3-thienyl)carbamate (295 mg), Pd(PPh3)4 (103 mg), 4-fluorophenyl boric acid (187 mg), and 1,4-dioxane (3 mL) was added a 2 M aqueous Na2CO3 solution (0.89 mL), followed by stirring under heating at 90° C. for 5 hours. The reaction mixture was diluted with water, and extracted with EtOAc. The organic layer was washed with water, and adjusted into pH=1 with 1 M hydrochloric acid. Next, the aqueous layer was washed with EtOAc and adjusted to pH=10 with an aqueous NaOH solution, and the aqueous layer was extracted with CHCl3. The organic layer was dried over MgSO4, and concentrated under reduced pressure. The residue was purified by basic silica gel column chromatography (manufactured by Fuji Silysia Chemical Ltd., YAMAZEN YFLC WPrep2XY, CHCl3). The collected fraction was concentrated under reduced pressure and the oil obtained was dissolved in EtOAc, followed by addition of 4 M HCl/EtOAc, concentration under reduced pressure, and solidification to dry. To the residue obtained were added EtOH and EtOAc for crystallization to obtain 1-azabicyclo[2.2.2]oct-3-yl [2-(4-fluorophenyl)-3-thienyl]carbamate hydrochloride (135 mg) as a white solid.

1. extractionextracted with EtOAc
2. washThe organic layer was washed with water
3. washNext, the aqueous layer was washed with EtOAc
4. extractionthe aqueous layer was extracted with CHCl3
5. dry with materialThe organic layer was dried over MgSO4
6. concentrationconcentrated under reduced pressure
7. customThe residue was purified by basic silica gel column chromatography (manufactured by Fuji Silysia Chemical Ltd., YAMAZEN YFLC WPrep2XY, CHCl3)
8. concentrationThe collected fraction was concentrated under reduced pressure
9. customthe oil obtained
10. customto dry
11. customTo the residue obtained
12. customfor crystallization