Triethyl phosphonoacetate → HCID 86603615, compound

HRID 2375992Notes

Reaction equation

HRID 2375992 reaction equation
[CH2:1]([O:3][C:4](=[O:14])[CH2:5]P(OCC)(OCC)=O)[CH3:2].[H-].[Na+].[Cl:17][C:18]1[CH:40]=[CH:39][C:21]([C:22]([N:24]2[CH2:29][CH2:28][CH:27]([NH:30][C:31]3[CH:38]=[CH:37][C:34]([CH:35]=O)=[CH:33][N:32]=3)[CH2:26][CH2:25]2)=[O:23])=[CH:20][CH:19]=1.C(OCC)(C)=O.O>C1COCC1>[Cl:17][C:18]1[CH:19]=[CH:20][C:21]([C:22]([N:24]2[CH2:25][CH2:26][CH:27]([NH:30][C:31]3[N:32]=[CH:33][C:34](/[CH:35]=[CH:5]/[C:4]([O:3][CH2:1][CH3:2])=[O:14])=[CH:37][CH:38]=3)[CH2:28][CH2:29]2)=[O:23])=[CH:39][CH:40]=1

Participants

6

Reactant 4

HCID 13345Triethyl phosphonoacetateHCID 24758Sodium hydrideHCID 22728543Water ethylacetateHCID 86095763HCID 86095763, compound

Product 1

HCID 86603615HCID 86603615, compoundYield 75.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
15 °C

Procedure

A solution of diethylphosphonoacetic acid ethyl ester (274 mg) in THF (10 ml) was added dropwise to a mixture of 60% sodium hydride in oil (55 mg) in THF (10 mL) with stirring at 10-20° C. under atmospheric pressure of nitrogen, and the reaction mixture was stirred at ambient temperature for 30 minutes. A solution of 6-{[1-(4-chlorobenzoyl)-4-piperidyl]amino}nicotinaldehyde (210 mg) in THF (10 ml) solution was added to the above mixture and resultant mixture was stirred at ambient temperature for 1.5 hour. The reaction mixture was poured into a mixture of AcOEt-H2O and the organic layer was washed with brine and dried over MgSO4. The solvent was evaporated in vacuo and the residue was chromatographed on silicagel eluting with AcOEt-MeOH (95:5). The eluted fractions containing the desired product were collected and evaporated in vacuo to give ethyl (2E)-3-(6-{[1-(4-chlorobenzoyl)-4-piperidyl]amino}-3-pyridyl)acrylate (190 mg)

Workup

  1. stirringthe reaction mixture was stirred at ambient temperature for 30 minutes
  2. stirringwas stirred at ambient temperature for 1.5 hour
  3. washthe organic layer was washed with brine
  4. dry with materialdried over MgSO4
  5. customThe solvent was evaporated in vacuo
  6. customthe residue was chromatographed on silicagel
  7. washeluting with AcOEt-MeOH (95:5)
  8. additionThe eluted fractions containing the desired product
  9. customwere collected
  10. customevaporated in vacuo

Sources & evidence

ORD record
ord-6692d42ad0f64467802780fcfde89422
Source dataset
uspto-grants-2008_12
Patent number
US07465731B2

Reaction notes

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