P,P,P′,P′-Tetraethyl P,P′-ethylidenebis[phosphonate] → HCID 131731112, compound

Temperature

-78 °C

As shown in FIG. 8, 2-Ethyl-3-iodo-imidazo[1,2-α]pyridine 72 (Example 28) (5.0 g, 18.34 mmol) in anhydrous THF (80 mL) was stirred at −78° C., under argon, then n-BuLi (2.5 M, 14.7 mL, 36.76 mmol) in hexanes was added slowly, keeping the temperature below −70° C. The resulting mixture was stirred for 10 minutes, then tetraethyl ethene-1,1-bisphosphonate 3 (5.52 g, 18.38 mmol) in anhydrous THF (20 mL) was added slowly , keeping the temperature below −70° C. The reaction mixture was stirred for an additional 10 min, cooled to room temperature, then quenched with saturated NH4Cl (100 mL). The mixture was then extracted with CH2Cl2 (200 mL×3) and the organic phase washed with water (200 mL×2). The resultant organic phase was then dried (NaSO4), concentrated under reduced pressure and purified on silica gel (CombiFlash, EtOAc/MeOH elution) and HPLC to afford [(diethoxy-phosphoryl)-(2-ethyl-imidazo[1,2-α]pyridin-3-yl)-methyl]-phosphonic acid diethyl ester 74 as pale yellow oil with a yield of 900 mg, 11%.

1. customthe temperature below −70° C
2. stirringThe resulting mixture was stirred for 10 minutes
3. customthe temperature below −70° C
4. stirringThe reaction mixture was stirred for an additional 10 min
5. temperaturecooled to room temperature
6. customquenched with saturated NH4Cl (100 mL)
7. extractionThe mixture was then extracted with CH2Cl2 (200 mL×3)
8. washthe organic phase washed with water (200 mL×2)
9. dry with materialThe resultant organic phase was then dried (NaSO4)
10. concentrationconcentrated under reduced pressure
11. custompurified on silica gel (CombiFlash, EtOAc/MeOH elution) and HPLC

ORD record

ord-5d8e2dfb9e564027a2f5539d4e8fbc1b

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08618079B2