Dimethyl methylphosphonate → [2-(5-Methyl-1-phenyl-1H-pyrazol-4-yl)-2-oxo-ethyl]-phosphonic acid dimethyl ester

HRID 2243902Notes

Reaction equation

HRID 2243902 reaction equation
[CH3:1][O:2][P:3]([CH3:7])(=[O:6])[O:4][CH3:5].[Li+].CCC[CH2-].C[O:14][C:15]([C:17]1[CH:18]=[N:19][N:20]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:21]=1[CH3:22])=O>C1COCC1.CCCCCC>[CH3:1][O:2][P:3]([CH2:7][C:15]([C:17]1[CH:18]=[N:19][N:20]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:21]=1[CH3:22])=[O:14])(=[O:6])[O:4][CH3:5]

Participants

6

Reactant 3

HCID 12958Dimethyl methylphosphonateHCID 61028n-Butyl lithiumHCID 827526Methyl 5-methyl-1-phenylpyrazole-4-carboxylate

Product 1

HCID 86609911[2-(5-Methyl-1-phenyl-1H-pyrazol-4-yl)-2-oxo-ethyl]-phosphonic acid dimethyl esterYield 86.4%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Conditions

Temperature
0 °C

Procedure

A solution of methyl-phosphonic acid dimethyl ester (2.1 g) in THF (20 mL) under an argon atmosphere was cooled to −78° C. and treated dropwise with 10.98 mL of a 1.6 M solution of N-butyllithium in hexane keeping the temperature of the reaction mixture below −65° C. After stirring for 15 minutes 5-methyl-1-phenyl-1H-pyrazole-4-carboxylic acid methyl ester (1.9 g in 2 ml THF) were added slowly and the mixture was stirred for 30 minutes (temperature below −65° C.). The reaction mixture was allowed to warm to 0° C., quenched with 1N aqueous HCl, and then partitioned between ACOEt and water. The layers were separated, the organic layer was washed with water, dried over MgSO4, filtered and evaporated to give [2-(5-Methyl-1-phenyl-1H-pyrazol-4-yl)-2-oxo-ethyl]-phosphonic acid dimethyl ester (2.34 g) as a dark brown oil that was used in the next reaction without further purification. MS (ESI): 309.1 (MH+).

Workup

  1. additionwere added slowly
  2. customquenched with 1N aqueous HCl
  3. custompartitioned between ACOEt and water
  4. customThe layers were separated
  5. washthe organic layer was washed with water
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. customevaporated

Sources & evidence

ORD record
ord-05fe8bd5f68548a596c55cd03652b4b7
Source dataset
uspto-grants-2010_03
Patent number
US07678795B2

Reaction notes

Loading…