Triethylamine → (1S,6R)-1-Amino-7-oxo-8-[(1R)-1-phenylethyl]-8-azabicyclo[4.3.0]non-3-ene

Triethylamine (1.61 mL, 11.5 mmol) and diphenylphosphoryl azide (1.62 mL, 7.52 mmol) were added to a solution of [(1S,6R)-7-oxo-8-[(1R)-1-phenylethyl]-8-azabicyclo[4.3.0]non-3-en-1-yl]carboxylic acid (1.65 g, 5.78 mmol) in toluene (28.9 mL) in a nitrogen atmosphere with stirring under ice-cooling, and the mixture was stirred at 100° C. for 30 minutes. The reaction solution was concentrated under reduced pressure, and triethylamine was azeotropically distilled with toluene (×3). 1,4-Dioxane (14.4 mL) and 4 mol/L hydrochloric acid (14.4 mL) were added to the resulting residue, and the mixture was stirred at 50° C. for six hours. The reaction solution was diluted with water (30.0 mL) and washed with ethyl acetate (50 mL×2). A 1 mol/L sodium hydroxide solution (55.0 mL) was added to the aqueous layer, followed by extraction with chloroform (100 mL×1, 80 mL×1). The organic layer was washed with brine (150 mL) and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure to give 1.24 g of the title compound as an amorphous.

1. temperaturecooling
2. stirringthe mixture was stirred at 100° C. for 30 minutes
3. concentrationThe reaction solution was concentrated under reduced pressure, and triethylamine
4. distillationwas azeotropically distilled with toluene (×3)
5. addition1,4-Dioxane (14.4 mL) and 4 mol/L hydrochloric acid (14.4 mL) were added to the resulting residue
6. stirringthe mixture was stirred at 50° C. for six hours
7. additionThe reaction solution was diluted with water (30.0 mL)
8. washwashed with ethyl acetate (50 mL×2)
9. additionA 1 mol/L sodium hydroxide solution (55.0 mL) was added to the aqueous layer
10. extractionfollowed by extraction with chloroform (100 mL×1, 80 mL×1)
11. washThe organic layer was washed with brine (150 mL)
12. dry with materialdried over anhydrous sodium sulfate
13. filtrationAfter filtration
14. concentrationthe filtrate was concentrated under reduced pressure

ORD record

ord-f694c4a43edd45bbb25831ea15a38bfd

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08618094B2