Dimethyl methylphosphonate → Dimethyl 2-oxo-2-(pyridazin-4-yl)ethylphosphonate

HRID 1527966Notes

Reaction equation

HRID 1527966 reaction equation
CO[C:3]([C:5]1[CH:10]=[CH:9][N:8]=[N:7][CH:6]=1)=[O:4].[CH3:11][P:12](=[O:17])([O:15][CH3:16])[O:13][CH3:14].C([N-]C(C)C)(C)C.[Li+]>C1COCC1>[O:4]=[C:3]([C:5]1[CH:10]=[CH:9][N:8]=[N:7][CH:6]=1)[CH2:11][P:12](=[O:17])([O:15][CH3:16])[O:13][CH3:14]

Participants

5

Reactant 3

HCID 12958Dimethyl methylphosphonateHCID 2724682Lithium diisopropylamideHCID 12439252Methyl pyridazine-4-carboxylate

Product 1

HCID 86684793Dimethyl 2-oxo-2-(pyridazin-4-yl)ethylphosphonateYield 29%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of methylpyridazine-4-carboxylate (1.00 g, 6.95 mmol) and dimethyl methylphosphonate (889 mg, 6.95 mmol) in THF (20 ml) was added a 2 M solution of lithium diisopropylamide (2 M in THF/heptane/ethylbenzene; 7.3 ml, 14.6 mmol) between −5° C. and 0° C. Then after 5 min the reaction mixture was carefully quenched with 4 M aq. hydrochloric acid solution to adjust the pH to ca. 6 and diluted with dichloromethane. The aqueous layer was separated and extracted 2 times with dichloromethane. The combined organic layers were washed with brine, dried over magnesium sulfate, filtered, and evaporated. Chromatography (SiO2; gradient ethyl acetate to ethyl acetate/methanol 9:1) afforded the title compound (460 mg, 29%). Dark red oil; MS: 231.1 [M+H]+.

Workup

  1. customThen after 5 min the reaction mixture was carefully quenched with 4 M aq. hydrochloric acid solution
  2. additiondiluted with dichloromethane
  3. customThe aqueous layer was separated
  4. extractionextracted 2 times with dichloromethane
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. customevaporated

Sources & evidence

ORD record
ord-bd2c1effb3f14f72a52dd93bfdeceaa2
Source dataset
uspto-grants-2015_07
Patent number
US09090565B2

Reaction notes

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