Diisopropylethylamine → (2S,5R)-2-[[(tert-butyldimethylsilyl)oxy]methyl]-3-methyl-6-(prop-2-en-1-yloxy)-1,6-diazabicyclo[3.2.1]oct-3-en-7-one

Temperature

-15 °C

Into a 2000-mL 3-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed a solution of (3R,6S)-6-[[(tert-butyldimethylsilyl)oxy]methyl]-5-methyl-N-(prop-2-en-1-yloxy)-1,2,3,6-tetrahydropyridin-3-amine (Intermediate 147, 8.4 g, 26.88 mmol, 1.00 equiv) in acetonitrile (1600 mL), N,N-Diisopropylethylamine (14.2 g, 109.87 mmol, 4.00 equiv). This was followed by the addition of a solution of ditrichloromethyl carbonate (2.9 g, 9.77 mmol, 0.40 equiv) in acetonitrile (100 mL) dropwise with stirring at −15° C. in 3 hr. The resulting solution was stirred overnight at room temperature. The resulting mixture was concentrated under vacuum. The resulting solution was diluted with 500 mL of ethyl acetate. The resulting mixture was washed with 2×400 mL of NH4Cl (aq.) and 2×400 mL of brine. The resulting mixture was concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:10). This resulted in 3.9 g (43%) of the title compound as yellow oil.

1. customInto a 2000-mL 3-necked round-bottom flask purged
2. temperaturemaintained with an inert atmosphere of nitrogen
3. stirringThe resulting solution was stirred overnight at room temperature
4. concentrationThe resulting mixture was concentrated under vacuum
5. additionThe resulting solution was diluted with 500 mL of ethyl acetate
6. washThe resulting mixture was washed with 2×400 mL of NH4Cl (aq.) and 2×400 mL of brine
7. concentrationThe resulting mixture was concentrated under vacuum

ORD record

ord-950db1813bcc454bbab1cd01c0dbcddb

Source dataset

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09309245B2