P,P,P′,P′-Tetraethyl P,P′-ethylidenebis[phosphonate] → HCID 131731110, compound

HRID 1916036Notes

Reaction equation

HRID 1916036 reaction equation
[CH2:1]([O:8][C:9]1[C:10]2[N:11]([C:15](I)=[CH:16][N:17]=2)[CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Li]CCCC.[CH:24]([P:34]([O:39][CH2:40][CH3:41])(=[O:38])[O:35][CH2:36][CH3:37])([P:26]([O:31][CH2:32][CH3:33])(=[O:30])[O:27][CH2:28][CH3:29])[CH3:25]>C1COCC1>[CH2:36]([O:35][P:34]([CH:24]([P:26]([O:31][CH2:32][CH3:33])([O:27][CH2:28][CH3:29])=[O:30])[CH2:25][C:15]1[N:11]2[CH:12]=[CH:13][CH:14]=[C:9]([O:8][CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)[C:10]2=[N:17][CH:16]=1)(=[O:38])[O:39][CH2:40][CH3:41])[CH3:37]

Participants

5

Reactant 3

HCID 11077490P,P,P′,P′-Tetraethyl P,P′-ethylidenebis[phosphonate]HCID 573552438-(Benzyloxy)-3-iodoimidazo[1,2-a]pyridineHCID 178418339Butyllithium

Product 1

HCID 131731110HCID 131731110, compoundYield 69%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

As shown in FIG. 6, 8-Benzyloxy-3-iodo-imidazo[1,2-α]pyridine 31 (Example 20).(7.0 g, 20 mmol) in anhydrous THF (200 mL) was stirred at −78° C., under argon, then n-BuLi (2.5 M, 16.0 mL, 40 mmol) in hexanes was added slowly, keeping the temperature below −70° C. . The resulting mixture was stirred for 10 min, then tetraethyl ethene-1,1-bisphosphonate 3 (6.0 g, 20.0 mmol) in anhydrous THF (20 mL) was added slowly, keeping the temperature below −70° C. The reaction mixture was stirred for an additional 10 minutes, cooled to room temperature, and 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 with Na2SO4, concentrated under reduced pressure and purified on silica gel (CombiFlash, EtOAc/MeOH elution) to afford [2-(8-Benzyloxy-imidazo[1,2-α]pyridin-3-yl)-1-(diethoxy-phosphoryl)-ethyl]-phosphonic acid diethyl ester 35 as yellowish brown oil. 7.18 g, 69% yield.

Workup

  1. customthe temperature below −70° C.
  2. customthe temperature below −70° C
  3. stirringThe reaction mixture was stirred for an additional 10 minutes
  4. customquenched with saturated NH4Cl (100 mL)
  5. extractionThe mixture was then extracted with CH2Cl2 (200 mL×3)
  6. washthe organic phase washed with water (200 mL×2)
  7. dry with materialThe resultant organic phase was then dried with Na2SO4
  8. concentrationconcentrated under reduced pressure
  9. custompurified on silica gel (CombiFlash, EtOAc/MeOH elution)

Sources & evidence

ORD record
ord-829870a0b47b46f7af393f954ae01225
Source dataset
uspto-grants-2013_12
Patent number
US08618079B2

Reaction notes

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