Triphenylphosphine → 2-bromo-N,N-diethylacetamide

Temperature

0 °C

Under a nitrogen atmosphere, N,N-diethyl-2-hydroxy-acetamide (42 mg, 0.320 mmol) was dissolved in dichloromethane (1.5 mL) and the mixture was cooled to 0° C. Triphenylphosphine (125.9 mg, 0.480 mmol) and N-bromosuccinimide (85.4 mg, 0.480 mmol) were added in order and the mixture was stirred at room temperature for 3.5 hours. The mixture was warmed to room temperature and 2-bromo-N,N-diethylacetamide was prepared in situ. To the mixture, solution of No. 5447725 (Compound G; 56 mg, 0.080 mmol) in dichloromethane (1.0 mL) was added dropwise under a nitrogen atmosphere. N,N-Diisopropylethylamine (69.7 μL, 0.40 mmol) was then added at room temperature, and the mixture was stirred under feflux for 14 hours. After completing the reaction, the mixture was extracted with dichloromethane. The organic layer was washed with water and a saturated brine and dried over anhydrous sodium sulfate. After the organic layer was filtered and the solvent was distilled off, the residue was then purified by HPLC (water with 0.05% TFA-acetonitrile with 0.05% TFA) to obtain 31.2 mg (42% yield) of the triester form.

1. temperatureThe mixture was warmed to room temperature
2. stirringthe mixture was stirred under feflux for 14 hours
3. customthe reaction
4. extractionthe mixture was extracted with dichloromethane
5. washThe organic layer was washed with water
6. dry with materiala saturated brine and dried over anhydrous sodium sulfate
7. filtrationAfter the organic layer was filtered
8. distillationthe solvent was distilled off
9. customthe residue was then purified by HPLC (water with 0.05% TFA-acetonitrile with 0.05% TFA)

ORD record

ord-e0344fdc5ceb4c62b70023929983546b

Source dataset

uspto-grants-2016_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09266853B2