Triphenylphosphine → 5,6-Dimethyl-2-nitro-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine

Temperature

0 °C

To a mixture of 250c (1.129 g, 5.27 mmol) and triphenylphosphine (4.14 g, 15.8 mmol) in anhydrous THF (40 mL) cooled at 0° C. was added the solution of di-isopropyl azodicarboxylate (DIAD) (3.19 g, 15.8 mmol) in THF (15 mL) over a period of 30 minutes while maintaining the internal temperature below 5° C. The reaction mixture was warmed to 30° C. and stirred at this temperature for 5 h. The mixture was then quenched with water (50 mL) and concentrated under reduced pressure. The residue was extracted with dichloromethane (3×80 mL). The combined organic layer was dried over Na2SO4 and filtered. The filtrate was concentrated under reduced pressure. The residue was purified by silica-gel column chromatography eluting with dichloromethane/methanol (80:1 to 30:1) to afford 250d (0.83 g, 80%) as yellow solid. MS-ESI: [M+H]+ 197.2

1. temperaturewhile maintaining the internal temperature below 5° C
2. temperatureThe reaction mixture was warmed to 30° C.
3. customThe mixture was then quenched with water (50 mL)
4. concentrationconcentrated under reduced pressure
5. extractionThe residue was extracted with dichloromethane (3×80 mL)
6. dry with materialThe combined organic layer was dried over Na2SO4
7. filtrationfiltered
8. concentrationThe filtrate was concentrated under reduced pressure
9. customThe residue was purified by silica-gel column chromatography
10. washeluting with dichloromethane/methanol (80:1 to 30:1)

ORD record

ord-88eba513e7994b4b84316d57cf41a0ca

Source dataset

uspto-grants-2016_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09238655B2