Diisopropylamine → tert-Butyl N-allyl-N-(2-isothiazol-5-yl-2-oxo-ethyl)carbamate

Temperature

-78 °C

To a −78° C. solution of diisopropylamine (9.01 mL, 64.01 mmol) in tetrahydrofuran (80 mL) is added n-butyl lithium (30.78 mL, 49.24 mmol, 1.6 M in hexanes) drop wise under nitrogen. The resulting solution is stirred at −78° C. for 20 minutes and then a solution of isothiazole (4.19 g, 49.24 mmol) in tetrahydrofuran (10 mL) is added drop wise. The resultant white slurry is stirred for 30 minutes at −78° C. A solution of tert-butyl N-allyl-N-[2-(methoxy(methyl)amino)-2-oxo-ethyl]carbamate (6.36 g, 24.62 mmol) in tetrahydrofuran (50 mL) is then added to the slurry over a 15 minutes period. The reaction is then stirred for 30 minutes at −78° C., warmed to ambient temperature and is stirred for 30 minutes. Saturated ammonium chloride (200 mL) is then added. The resulting solution is extracted three times with ethyl acetate. The combined organic layers are dried over sodium sulfate, filtered, and concentrated under vacuum. The crude product is purified over silica gel with a 35 minute, 5% to 100% ethyl acetate in hexanes gradient, to give the title compound (6.00 g, 21.25 mmol, 86%). ES/MS (m/e): 283.0 (M+H).

1. stirringThe resultant white slurry is stirred for 30 minutes at −78° C
2. stirringThe reaction is then stirred for 30 minutes at −78° C.
3. temperaturewarmed to ambient temperature
4. stirringis stirred for 30 minutes
5. extractionThe resulting solution is extracted three times with ethyl acetate
6. dry with materialThe combined organic layers are dried over sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated under vacuum
9. customThe crude product is purified over silica gel with a 35 minute

ORD record

ord-0cc50b9088fd45ffb8e845975326eff2

Source dataset

uspto-grants-2014_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08889856B2