Ethanol → (3R,4R,5S)-4-amino-5-azido-3-(1-ethyl-propoxy)-cyclohex-1-enecarboxylic acid ethyl ester

Temperature

80 °C

To a solution of 300 mg of 26 and 1.25 mL EtOH in a 5.0 mL round-bottom flask equipped with a magnetic stirrer, a reflux condenser and an inert gas supply was added 0.31 mL of 96% sulfuric acid. The black solution was stirred for 18 h at RT and 8 h at 80° C. The black reaction mixture was cooled to RT treated with 8.0 μL of a mixture of 65 mL ammonium hydroxide 25% and 435 mL of brine, and extracted with 9.0 mL of EtOAc. The separated organic phase was washed with 10 mL of water and the water phase was back-extracted with 9.0 mL of EtOAc. The combined organic phases were dried (Na2SO4, 20 g), filtered and evaporated at 40° C./140-10 mbar to afford 175 mg crude product as a dark brown oil. The crude product was purified by SiO2 column chromatography eluting with EtOAc containing 1% v/v of 25% aqueous ammonium hydroxide. The combined fractions were evaporated at 40° C./140-10 mbar to afford 97 mg of 28 as a brown oil.

1. customThe black reaction mixture
2. temperaturewas cooled to RT
3. extractionextracted with 9.0 mL of EtOAc
4. washThe separated organic phase was washed with 10 mL of water
5. extractionthe water phase was back-extracted with 9.0 mL of EtOAc
6. dry with materialThe combined organic phases were dried (Na2SO4, 20 g)
7. filtrationfiltered
8. customevaporated at 40° C./140-10 mbar
9. customto afford 175 mg crude product as a dark brown oil
10. customThe crude product was purified by SiO2 column chromatography
11. washeluting with EtOAc containing 1% v/v of 25% aqueous ammonium hydroxide
12. customThe combined fractions were evaporated at 40° C./140-10 mbar

ORD record

ord-2ff10248a2a0461d97139e68361d0f9d

Source dataset

uspto-grants-2009_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07531687B2