Triethyl phosphonoacetate → ethyl (2E)-3-{6-[(1-benzyl-3-pyrrolidinyl)amino]-3-pyridyl}acrylate

HRID 226296Notes

Reaction equation

HRID 226296 reaction equation
[CH2:1]([O:3][C:4](=[O:14])[CH2:5]P(OCC)(OCC)=O)[CH3:2].[H-].[Na+].[CH2:17]([N:24]1[CH2:28][CH2:27][CH:26]([NH:29][C:30]2[CH:37]=[CH:36][C:33]([CH:34]=O)=[CH:32][N:31]=2)[CH2:25]1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.C(OCC)(C)=O.O>C1COCC1>[CH2:17]([N:24]1[CH2:28][CH2:27][CH:26]([NH:29][C:30]2[N:31]=[CH:32][C:33](/[CH:34]=[CH:5]/[C:4]([O:3][CH2:1][CH3:2])=[O:14])=[CH:36][CH:37]=2)[CH2:25]1)[C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1

Participants

6

Reactant 4

HCID 13345Triethyl phosphonoacetateHCID 24758Sodium hydrideHCID 22728543Water ethylacetateHCID 860957836-[(1-Benzyl-3-pyrrolidinyl)amino]nicotinaldehyde

Product 1

HCID 86603613ethyl (2E)-3-{6-[(1-benzyl-3-pyrrolidinyl)amino]-3-pyridyl}acrylateYield 88.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
15 °C

Procedure

A solution of diethylphosphonoacetic acid ethyl ester (896 mg) in THF (10 ml) was added dropwise to a mixture of 60% sodium hydride in oil (170 mg) in THF (20 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-benzyl-3-pyrrolidinyl)amino]nicotinaldehyde (0.75 g) in THF (10 ml) solution was added 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-benzyl-3-pyrrolidinyl)amino]-3-pyridyl}acrylate (0.83 g).

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-af360d6793264817afd2036d1fc70093
Source dataset
uspto-grants-2009_07
Patent number
US07557127B2

Reaction notes

Loading…