Triethylamine → (1S,5S)-1-Amino-7-methylene-4-oxo-3-[(1R)-1-phenylethyl]-3-azabicyclo[3.3.0]octane

Triethylamine (0.489 ml, 3.50 mmol) and diphenylphosphoryl azide (0.491 ml, 2.28 mmol) were added to a solution of [(1S,5S)-7-methylene-4-oxo-3-[(1R)-1-phenylethyl]-3-azabicyclo[3.3.0]octan-1-yl]carboxylic acid (500 mg, 1.75 mmol) in toluene (8.75 ml) in a nitrogen atmosphere with stirring under ice-cooling. The mixture was stirred at room temperature for 30 minutes and then at 100° C. for 30 minutes. The reaction solution was concentrated under reduced pressure, and triethylamine was azeotropically removed with toluene (×3). 1,4-Dioxane (4.37 ml) and 6 mol/L hydrochloric acid (4.37 ml) were added to the resulting residue, and the mixture was stirred at 50° C. for one hour. The reaction solution was diluted with water (18.0 ml) and washed with diethyl ether (60 ml×2). The aqueous layer was made alkaline with a 1 mol/l sodium hydroxide solution, followed by extraction with chloroform (80 ml×1, 70 ml×1). The organic layer was washed with water (80 ml) and brine (80 ml) and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure to give 238 mg of the title compound.

1. temperaturecooling
2. stirringThe mixture was stirred at room temperature for 30 minutes
3. concentrationThe reaction solution was concentrated under reduced pressure, and triethylamine
4. customwas azeotropically removed with toluene (×3)
5. addition1,4-Dioxane (4.37 ml) and 6 mol/L hydrochloric acid (4.37 ml) were added to the resulting residue
6. stirringthe mixture was stirred at 50° C. for one hour
7. additionThe reaction solution was diluted with water (18.0 ml)
8. washwashed with diethyl ether (60 ml×2)
9. extractionfollowed by extraction with chloroform (80 ml×1, 70 ml×1)
10. washThe organic layer was washed with water (80 ml) and brine (80 ml)
11. dry with materialdried over anhydrous sodium sulfate
12. filtrationAfter filtration
13. concentrationthe filtrate was concentrated under reduced pressure

ORD record

ord-a9dd50c3f16f468b91dc9f8a8c8ec01d

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08618094B2